Jon's Hairy Cell Leukemia (HCL) Blog

Mission Accomplished!

2011-07-07T08:15:00.000-07:00

I was going to call this post "A Little Bit of Everything", but fortunately my plans have changed!

I did it!, or should I say "Dr. Kreitman and The NIH Trial to Treat First Time HCL Patients did it!" All of my tests are now negative: peripheral blood flow (looks for hairies in your veins), bone marrow and most importantly bone marrow aspirate (the liquid in your bones where cells develop) are all negative! I couldn't have done it without the NIH trial. If you recall, it's taken me a little over two years to get here.

The initial treatment with Cladribine only led to a partial remission, and I still had 30% bone marrow infiltration and positive blood flows at 6-months post-chemo (November 2009). At that point, I had my first Rituxan treatment (8 rounds over 8 weeks). I achieved a complete remission (CR) 6 months later, in May 2010, but still had hairy cells in my bone marrow aspirate (a value not included in determining CR). That 1st CR was short lived. The cells in my aspirate continued to proliferate and upon restaging in December 2010, my bone marrow infiltration was back up to 5% and the peripheral blood flow showed .04% hairies. Although my complete blood counts (CBCs) were at remission levels, the marrow infiltration indicated it was no longer a CR and positive flow results for hairy cell indicated minimal residual disease (MRD), so I was retreated with Rituxan for the second and final time in accordance with the trial's protocol. This latest treatment wiped out the hairies in all areas to undetectable levels. I'm not completely out of the woods. Time will tell if this is a durable remission, but one thing's for sure: The combination of Cladribine and Rituxan did what Cladribine alone could not without waiting for relapse or subjecting me to multiple rounds of chemo.

Although I've wiped out the hairies, I have one more minor hurdle to jump. As I discovered and wrote last year, there is a documented phenomenon that occurred in 20% of lymphoma patients, who received combined chemo and Rituxan therapy, known as Rituxan-related late onset neutropenia (LON). The nadir (low point in counts) typically occurs 14 weeks after the last dose of Rituxan when the counts dip to about 660 (average). The effect lasts for about 4 weeks. I noticed a similar effect happened to me after my first Rituxan treatment and blogged about it then. You'll also recall that I've been interested in seeing if it would happen again. Well, it happened again! My 6-month CBC (16 weeks after my last Rituxan dose or 24 weeks after I started this cycle) indicates that my neutrophils are at 750. Although it appears to be slightly later by 2 weeks, I don't get CBCs often enough to say whether the low-point occured at 14 weeks or not.

Still, it is statistically in keeping with the findings of the lymphoma study. I believe I've discovered and am the first documented case of this occuring in an HCL patient. Time will tell as my recovery and other patients are studied. I expect to be at a remission level in 3 weeks, when I have my next CBC. So technically, I'm not in a CR until the neuts jump back up, but I don't really care. Everything else is in great shape. Based on my first experience and knowledge of RTX LON, I consider it a nuance that will quickly recover; however, I won't be surprised if the duration of this neutropenia is slightly longer than the first time.

So far it's been a great summer. My youngest daughter, who was born a year after I was first treated, started walking on her first birthday and can now say the letters in her name. My 3-year old is doing great and having lots of fun with her garden and playing in the sand and taking swim lessons. We recently headed up to Lancaster, PA to visit Dutch Wonderland and the Thomas the Train event at Strasburg railroad in our new Swagger Wagon (a Honda Odyssey). My nephew was inducted into the US Naval Academy and was personally sworn in by Cpt. Frank L. Culbertson, former commander of the international space station and the space shuttle. It was a very proud and moving moment.

The sun and I have also come to terms. I'm going to wear sunscreen and s/he's going to lay off me for awhile. Likewise, I've set up a portable 60 Watt solar panel array to charge all my mobile devices and run my low power electronics to pay her/him hommage. Yes, I'm a gadget geek, but if the power ever goes out, I'll still have my iTunes! I also just bought a kayak and will be taking lots of late afternoon trips on the Potomac this summer.

Yippeekayay !!!

All Hail Ra

2011-06-10T11:46:00.000-07:00

I know it's been too long since my last post!

I've got lots to discuss and I'm short on time right now, but I wanted to share an interesting "Science Daily" article that I just found.

http://www.sciencedaily.com/releases/2011/06/110608195159.htm

It states:

The researchers demonstrated that B-cells are deficient in one of the main DNA repair pathways, known as Nucleotide Excision Repair. This pathway repairs a lot of different DNA lesions, including UV-induced damage and chemical adducts (e.g. from air pollution and cigarette smoke). Their model therefore explains why strong UV exposure (e.g. unprotected sun bathing) is the number one environmental risk factor for lymphoma and also supports the evidence that exposure to air pollution and smoking are also risk factors.

Dr Nouspikel said: "Lymphoma is one of the ten most frequent cancers in adults in the UK, and the third among children. If we want to come up with efficient strategies for prevention and therapy, it is crucial to understand what causes it. The novel mechanism we have discovered potentially accounts for the development of many different types of lymphoma. It may also explain why strong exposure to sunlight is the main environmental risk factor for this cancer."

This supports my theory than sunlight may cause mutations (specifically cytosine deamination to uracil in RNA) that cause HCL! Likewise, it reinforces my hypothesis that the reason they can't sequence my hairy cell DNA is because there is a mutation in my DNA corresponding to the primer they're using which the DNA repair enzymes either failed or don't attempt to repair.
I've got lots more to talk about, like mcl-1 inhibitors and new data at 15 weeks after my last Rituxan treatment that supports my Rituxan-related late onset neutropenia (LON) hypothesis, but it'll have to wait until I have more time. I'm still waiting to get my latest flow results.

There was a huge Coronal Mass Ejection (CME) 2 days ago that spanned half the surface of the sun and is headed our way, so wear sunscreen!

Later.
6/11/2011 update

Wow! Just one day later, one of my fellow HCL'ers (shout out to Vincent) found this announcement:

http://www.medpagetoday.com/HematologyOncology/Leukemia/27009

It states that HCL has been narrowed down to a single common gene mutation, BRAF V600E. BRAF is a gene most widely known for its involvement in melanoma. This is groundbreaking, and since the leading cause of BRAF V600 mutation is excessive sun exposure, gives further credence to my hypothesis that sun exposure is a leading cause of HCL. All these studies are starting to add up and reinforce that hypothesis. It also means that clinical trials with BRAF V600E inhibitors like PLX-4720, which are highly active in treating melanoma, are warranted in patients with refractory and relapsed HCL. Perhaps a PLX4720-assisted Cladribine / GA-101 trial in refractory and relapsed HCL'ers is in the future...

Here's the published study.

These findings may lead to the development of mouse models for HCL research:

"On the basis of our findings, it should be feasible to develop murine models of HCL by activating the RAS–RAF–MAPK signaling pathway in specific B-cell subpopulation."

"Strikingly, a T→A transversion occurring at position 1860 of the messenger RNA RefSeq NM_004333.4 and resulting in the V600E variant was found in samples from all 47 patients with HCL..."

I'm hypothesizing that the transversion is sunlight induced. It will be interesting to see if research related to the first study I cited can determine whether DNA excision repair related to BRAF V600 is inactive during certain stages of B-cell maturation (specifically en route or at the germinal center stage).

It's all coming together. Needless to say Eddie Vedder's "Hard Sun" is going to be the backup soundtrack for my next bloodcount video...

I Got Chills...They're Multiplyin' ...

2011-04-03T07:04:00.000-07:00

You've got to be kidding me!!! Two flus in 1 month ???!!!!

I couldn't believe it. The baby came down with flu A on February 28th.  I started developing symptoms 2 days later and went to see my PCP. The quick flu test was negative, and it's supposed to be accurate to 90+%, so he told me it was probably a bacterial infection. Still, they did a culture to be on the safe side.  I started back on Tamiflu just to make sure I wouldn't get the flu again since the baby had it. That night, I sweated profusely, just like with flu B two weeks prior. I was skeptical that I didn't have the flu, and I continued to feel pretty lousy the rest of the week -- fevers up to 102, etc.

That Saturday, my PCP sent me a message saying it WAS flu A, so I increased the Tamiflu dose to 2 pills a day. It seemed to do little good, and I took over a week to recover. I later read that flu A can mutate to isolates that don't respond to Tamiflu (it says so on the info packet), so I assume that's what happened. My recovery from flu B was much faster and had far less Tamiflu-related nausea.

I just had my 3 month Rituxan follow up on March 28th. The blood counts are looking great! The WBC is almost back to normal for a normal person, and that's pretty good considering how low my lymphocyte count still is. Since the hairy cells are B-lymphocytes, you want that count (aka "ALC") to be low.  My neutrophils are holding steady, and my monocytes are really doing well. I'm sure that getting the flu twice in 1 month didn't hurt getting the monocyte count up, but they're still high 1 month later, so I'm not complaining.  Hopefully, that will assist the ADCC mediated by Rituxan and kill more hairies.

I've lost a lot of time at work dealing with the two flus and taking care of the baby. She's had chronic ear infections for several months in addition to the flu.  She's finally going to get ear tubes on Monday. It worked wonders for her big sister, so we're looking forward to it.

Here's the latest video of my blood counts. Overall, I'm really happy with the results, but my phosphorus level has dipped below normal several times since RTX#2. I'm not sure if that has to do with marrow replenishment or over-excretion in the urine due to a vitamin D deficiency. Time will tell, but if it continues to trend downward, I may consult a endocrinologist and try to find out what's causing it.

In other news, it looks like things may be moving forward with a Rituxan vs. GA-101 trial for Hairy Cell in refractory and relapsed patients! GA-101 is the Type II anti-CD20 antibody I found in September, while studying "lipid rafts", and brought to Dr. K's attention. It's engineered to have a wider elbow angle which is able to mediate cell death 5 to 100 times more effectively than Rituxan. It's also less toxic. I'll let you know as I find out more.

Here's a table of drugs for which I'd like to see more data regarding effectiveness in treating HCL:

Rituxan, Flu and a Spike in Counts too ...

2011-02-26T15:22:00.000-08:00

I've been holding off this post until I had enough new data to share to make it worthwhile, but I didn't realize I'd get the flu while I was waiting. Between treatments 6 and 7, I got hit hard with influenza B. No doubt my youngest brought it home from daycare. The youngest had a mild fever two days before I came down with it. Fortunately, everyone (including myself) had been vaccinated earlier in the season, but since I've anihilated my B-cells, there wasn't much benefit left from the vaccine. I started feeling aches on that Saturday, but it didn't hit hard until Superbowl Sunday. I got in bed around 10 am, couldn't really move and stopped drinking enough fluids. Once my fever spiked to 102 around 3 pm, I called the NIH day hospital, and they asked me to come in.

I got to Bethesda around 4:30 pm. My fever went up and down between 98 and 103 several times while there. They ran CBC, chemistry and cultures and hooked me up to an IV. 4 hours, 3 bags of saline and a digital X-ray later, I was good to go with Tamiflu and Tylenol in hand. The next morning at 6 am, I started sweating profusely on my upper body. At 7 am, I was awake enough to take off my T-shirt, which I could have rung out to get a couple cups of water in a bucket. I continued to have roller coaster fevers for the remainder of the day, but my temperature finally recovered later that evening, and I was able to go back to NIH the next day (Tuesday) to receive treatment #7.

Needless to say, my counts spiked as shown above. On the plus side, I had a normal WBC for the first time since collecting counts. Same with the platelets. I'm hoping the short term boost may have benefited my ADCC response to the Rituxan treatments too. It can't hurt to have all those extra neutrophils and monocytes available to recognize and target the hairy cells...

Lots of HCL patients have anecdotally commented that when they got viral infections, their counts improved for awhile; however, my response was short-lived and only lasted as long as the viral infection. One exception -- my platelets seem to have gotten a significant and more durable boost, and are at the best level I've ever measured. Hopefully, that's a sign of good things to come.

I've got lots more to add to this post, including another potential treatment that uses a protein known as CD-19L, found on T cells, to kill leukemia cells that express CD19. Scientists have now bioengineered CD19-L in a solution without T-cells and shown it to kill ALL cells in vitro. Since hairy cells express CD19 too, I'm hoping CD19-L will bind to and destroy them. Hopefully, this bioengineered protein will continue to be developed and result in treatments for ALL and possibly HCL too.

I've been studying somatic hypermutation (SHM) associated with the variable heavy-chain region of B-cell immunoglobulins and wondering if the random production of Ig antibody is somehow associated with HCL mutations. This has led me to postulate some new theories on the cause of HCL. I think HCL may be caused by RNA cytosine nucleoside exposure to sunlight that results in deamination of cytosine to uracil. Next thing you know, the alteration causes a protein to fold improperly, chromosomes mix with the wrong crowd, locks get picked with mutated keys and genes start translocating all over the place. Before you know it, you've got just the right random blend of mishaps and a self-sustaining HCL mutation on your hands.

Dr. John Sutherland, a Professor of Organic Chemistry at the University of Manchester, England has recently shown that RNA may be the starting point for life and that sunlight alone can deaminate cytosine in RNA to uracil. This was discussed on a recent episode of NOVA Science Now. I wonder if sunburn inflammation and UVA/UVB exposure as some B-cells divert through capillaries on their way from the marrow to the germinal centers could cause hairy cell leukemia mutations? Hairy cellers are generally active, outdoor-types and tend to engage in activities that can result in excessive sun exposure. White males with fair traits have the greatest incidence of classic HCL. Likewise, HCLers have a higher incidence of basal cell carcinoma (BCC), another disease associated with people with fair traits and excess sun exposure.

      My HCL recipe:
          Ingredients:
               one part genetic disposition (fair trait genes)
                age
                excessive UVA/UVB or sunburn (or maybe high frequency RF since electrical engineers have 8x more incidence than most people)
           Directions:
                 Mix well until random RNA cytosine deamination causes a protein production train wreck and HCL-related gene translocations.

Perhaps patients that have a durable remission beyond 15 years but then relapse aren't really relapsing, but instead have a new HCL mutation caused again by excessive sun exposure. Sequencing and comparing the patients' HCL DNA at initial diagnosis and the later onset would determine if the relapse is a clone of the original occurence or derived from a new progenitor.

I wonder if the difficulty in sequencing my hairy cell DNA and generating a PCR primer might be due to an unusually rare cytosine deamination to uracil in my DNA (rather than RNA) that the DNA repair enzyme somehow freakishly failed to catch and repair. I'm hoping they make some progress soon and can tell me what's different about my sequence. Regardless, I'm exceedingly grateful for the opportunity to participate in the NIH clinical trial, and all the effort and help Dr. Kreitman and his staff have put into helping me.

Now that I've completed all the treatment provided by this trial, I'm in the watchful waiting stage -- anxiously looking forward to my next bone marrow biopsy and aspiration in June. Hopefully this time, I'll be negative for hairies on all three tests -- peripheral blood, bone marrow and aspirate.

Wish me luck!

Hairy Cell Trivia

2011-01-23T19:12:00.000-08:00

Thought I'd put together a few trivia questions for those of you who want to test your hairy cell leukemia knowledge:

Questions:
1) What type of cells are hairy cells believed to come from?
2) Who discovered hairy cell leukemia?
3) In what year was hairy cell leukemia discovered?
4) Where was hairy cell leukemia discovered?
5) What is the formal name of hairy cell leukemia?
6) What protein is overexpressed on hairy cells and the main target of monoclonal antibody therapy?
7) What does the "CD" in "CD20" stand for?
8) Name the primary chemotherapies for hairy cell leukemia?
9) When is Pentostatin typically used in lieu of Cladribine?
10) What's the term for treatment with a monoclonal antibody (mAb)?
11) What is the primary mAb used to treat hairy cell?
12) What other surface proteins are also targeted in hairy cell?
13) Name a well known HCL immunotoxin?
14) Who is Ira Pastan?
15) What is the bacterial toxin used in HA22, and what's its origin?
16) What is the typical cause of fever after treatment with Cladribine (commonly misdiagnosed as "a mystery infection")?
17) What are the three modes of cell death mediated by Rituxan?
18) Who invented Cladribine?
19) Which is the more effective approach for administering Cladribine?
              5 day x 2 hour IV
              or 24x7 drip?
20) At what stage of cellular development is the malignant mutation of hairy cell believed to occur?
21) What is the median age of an HCL patient at diagnosis?
22) Is HCL more prevalent in men or women?
23) What causes the "classic" version of hairy cell leukemia?
24) What is the average period of remission for HCL after Cladribine chemotherapy?
25) What percentage of patients receiving Cladribine have a complete remission, partial remission, and no response?
26) How rare is hairy cell leukemia?
27) What does MRD stand for?
28) Is there a cure for hairy cell leukemia?
29) The first case of patient/doctor genetic rights involved hairy cell leukemia and what university?
30) What's the life expectancy of the average hairy cell leukemia patient?
31) When should hairy cell leukemia be treated?

Answers:
1) B-cells, a type of lymphocyte.
2) Bertha A. Bouroncle, MD
3) 1958
4) Ohio State University
5) Reticuloendotheliosis
6) CD20
7) "Cluster of Differentiation"
8) Cladribine and Pentostatin
9) When a patient's counts are so low or health is so weak that a less sudden drop in counts is needed; however, it is sometimes used if a patient doesn't respond to Cladribine. Pentostatin is administered over several weeks whereas Cladribine is administered in 5 or 7 days.
10) mAb therapy
11) Rituximab (aka: Rituxan)
12) CD25, CD22
13) HA22
14) Head of NCI laboratory of molecular biology and immunotoxin development
15) Pseudomonas Exotoxin from Pseudomonas aeruginosa
16) Tumor Lysis (hairy cells dying)
17) Apoptosis (cell suicide), antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC)
18) Dr. Dennis Carson
19) Both are considered equally effective
20) Later in the differentiation process at the level of the germinal center B-cells, likely in the process of differentiating to a Memory B-cell (per Basso, et al, p.62, col 1).
21) 52
22) Men, by a ratio of 4:1
23) Most cases of classic HCL have a BRAF V600E DNA mutation, caused by photons from sunlight causing a RNA/DNA translation in a B-cell during replication. This mutation is also common to 50% of melanoma cases, but in that case, it affects a skin cell.
24) Ten years.
25) 80%, 15% and 5% respectively.
26) HCL accounts for only 2% of diagnosed/reported cases of leukemia. However, it may be more prevelant since it can remain "in-check" in many people without ever being diagnosed.
27) Minimal Residual Disease.
28) Not yet, but there are hairy cell clinical trials trying to establish a cure curve.
29) UCLA (link to court case)
30) The average patient will have a normal life expectancy.
31) In general, HCL should be treated when blood counts indicate one of the following conditions:
                 Platelets (PLT) < 100 K/uL
                 Hemoglobin (HGB) < 10 g/dL
                 Absolute Neutrophils (ANC) < 1.0 K/uL
       however, Dr. Michael Grever, in his paper "How I treat Hairy Cell Leukemia (Blood, 10/2009)" states the following:

"Therefore, I recommend that therapy be initiated when a declining trajectory predicts that the patient will reach a platelet count less than 100,000/uL or an absolute granulocyte count consistently below 1,000/uL."

Kinected

2011-01-18T19:16:00.000-08:00

A lot has happened since my last post:

Christmas
New Years
Birthdays (Howard Recombinant DNA Experiment #1 turned 3, and my wife had a birthday too)
4 Rounds of Rituxan

The Rituxan treatments have gone well, although I've had to deal with several failed IV placements (including 3 blown veins). The only significant change in my blood counts so far has been a dramatic increase in monocytes as shown below, but this has me very excited. It's believed that monocytes may mediate the antibody-dependent cell-mediated cytotoxicity (ADCC) by Rituximab, and a cursory analysis of my counts leads me to believe this may be the case. Specifically, my monocyte counts increased dramatically after both Rituxan treatments were initiated (see highlighted areas).

I believe this increase in monocytes is directly correlated to the administration of the Rituxan as they begin to kill the hairies through antibody attack (see picture below). The monocytes increase in numbers as Rituxan (RTX) is introduced into the bloodstream and then they level off as they morph into phagocytes and ADCC is evoked. As you can see in the highlighted areas above, the pattern for this cycle (RTX #2) is similar to the first RTX treatment in 2009, but the initial level of monocytes is much higher. Given that my spleen is now 40% of its prior volume (no longer infiltrated with hairies), and the monocyte level is 9 times higher than when I started RTX treatment #1, I think this round may have a much bigger impact in reducing the hairy cell burden in my marrow aspirate!

Monocyte Mediated ADCC

Starting in week 5 of RTX treatment #1, my neutrophil level increased dramatically as the monocyte levels began to top off. Hopefully, the same increase will occur over the next few weeks. If so, I think the response correlation with RTX treatment #1 will be another strong indicator of monocyte mediated ADCC. It may take awhile for it to complete the job, but fortunately Rituxan's half-life is two weeks, so it will remain in my bloodstream for months and during that time > 99% remains in the peripheral blood looking for B-cells and hairies to destroy, so it's readily available for quite awhile as the layers of the hairy clumps are peeled away.

Then again, since neutrophils are the first to attack (neutrophils are microphages, ie: small eaters), they may be pulled out of the peripheral blood stream to mediate Rituxan-induced complement-dependent cytoxicity (CDC) and attach to C3b proteins -- causing a drop in their blood levels. Perhaps the monocytes are being released into my blood stream in response to the transient decrease in neutrophils. Monocytes are held in reserve in the splenic red pulp for just such an emergency. As the monocytes morph into macrophages (ie: big eaters) to mediate ADCC induced by Rituxan, the neutrophils are no longer needed as much and stay in the blood and increase in numbers as marrow function improves.

I watched the Dr. Najeeb lecture series on the complement system, and now I'm wondering if an overzealous complement system response to Rituxan aggregates immune complexes (Ig's, anaphylatoxins like C3a, mast cell activation products, etc.) in the skin that lead to the non-itchy rashes often seen in patients who take Rituxan. I had several during my first round in 2009. This cycle I noticed a small dime-sized one on my left arm a couple days after the first round that's still there. They're small patches that usually take 5 to 8 weeks to clear.

Here's a video on Rituxan's mode of action that covers direct cell death, ADCC and complement. However, the video indicates NK cells are responsible for ADCC whereas I'm postulating that monocytes may also play a significant role.

My fascination with GA101 continues to grow. It's a third generation monoclonal antibody (mAb) that mediates ADCC 5 to 100 times more effectively than Rituxan. Not only is this antibody humanized, but it's elbow region has been engineered to provide better cross-linking of CD-20 antigens, which appears to dramatically improve apoptosis (cell suicide) as stated in a citation from a prior post. This mAb has now undergone Phase II trials in indolent/refractory non-Hodgkin's lymphoma with very good results. I'm lobbying and anxious for in-vitro studies to occur in HCL.

[Credit: Robert Marcus, Kings College Hospital, London]

Aside from that, I've become quite a gadget geek. I bought a PS3 to support my http://folding.stanford.edu/ hobby and an Xbox Kinect for working out. It's seems to be doing the trick too. My creatine kinase levels went from 109 to 315 over the past week. CK is an enzyme that's secreted when you workout and convert ATP to ADP to release energy. The Kinect is an imaging sensor that allows you to play games without a controller. It's truly amazing. The technology is still in its infancy, but you can use it to workout and keep/manage all your workout metrics, and it provides real-time analysis of your form that's better than a personal trainer's. I predict it will make P90x obsolete within a year, and I'm anxious for a yoga application to be released. I'm hoping some yoga and regular stretching will keep things fluid in my marrow and increase the hairy clump surface area to volume ratio, but that's just a WAG. I figure it can't hurt.

I'm so grateful and glad I'm participating in the NIH clinical trial! Not treating my somewhat difficult case with Rituxan by monitoring MRD would probably have led to more Cladribine treatments and marrow suppression. I think that my case shows that just blindly adding Rituxan at 6 months post-Cladribine and taking a wait-and-see approach by monitoring counts to determine relapse is risky -- especially for younger patients. Rather, monitoring and treating MRD is the way to go, and right now, only NIH has the facilities to do that -- especially the hypersensitive PCR MRD test. Likewise, NIH provides 2 8-week cycles of Rituxan to treat MRD -- something regular oncologists won't be able to justify to insurance companies until the NIH study is completed.

The family's doing well. My youngest (8 mo's) is already cruising and lifting herself up on tables, and the eldest is starting to read and play computer games (Dora and Cat in the Hat). I've had a couple weeks as Mr. Mom over the past month while my wife's been on travel. The first time was a breeze, but the baby had an earache the second time, so things were a little more exhausting. I've been working on Ka-band science downlink designs for future Deep Space Discovery Missions and the S-band command and telemetry link for the GEMS program. Overall, things are going well.
Happy New Year, and here's to a fruitful 2011!

Rewind...

2010-12-23T15:35:00.000-08:00

I had a clinic appointment yesterday and got my FACS and BMBx results:

Peripheral blood flow is unchanged over the past 3 months and holding at .04% hairies.
Aspirate flow is at 4% -- up from 2% last May.
BMBx immunostaining shows 5% infiltration. That means I'm no longer in remission.

It could be that my aspirate and blood flows always had hairies, but they were just masked by Rituxan until it detached from the cells and flushed out of my system. Still, the Rituxan treatments had an effect. Prior to Rituxan, my bone marrow infiltration at 6 months post-chemo was 30%. Now it's just 5%. Likewise, my blood counts are now about the best they've been since treatment started and they got a real boost after the Rituxan treatments.

The protocol calls for another round of Rituxan treatments at 6 months post-Rituxan if the peripheral blood flow is positive, so I'll be going in to NIH next Tuesday to get some more aspirate drawn for the PCR lab, then I'll start the first of 8 more Rituxan treatments (1 a week for 8 weeks) in the early afternoon.

The basic gist is this: given that my hairies' DNA doesn't bind to the baseline PCR primer used for the hyper-sensitive MRD analysis (and any variants they may have tried), my HCL genome is likely mutated from the norm such that they don't die as easily as most, even though they have more than 100,000 CD20 antigens and bind really well with the Rituxan. The exact nature of the mutation is still not known.

Since I was slow in responding to Cladribine and didn't get a knock-out punch from Rituxan, I wonder if the assumed mutation affects lipid raft function and restricts the biochemical reaction associated with hairy cell apoptosis and antibody-dependent cellular cytotoxicity (ADCC), but there's no way to know that for sure (for now anyway). Likewise, the high and fairly steady flow in the aspirate leads me to wonder if there is a significant physiological change or maturation of the cells as they move from the aspirate into the marrow and peripheral blood that makes the pb and marrow cells easier to kill (a more normal lipid raft structure)? Regardless, the prevailing theory is that the hairies in the aspirate are clumped together in a ball and the Rituxan can't peel away enough layers of the onion to eliminate them completely.

In any case, I'm hoping this round will provide more of a wallop since the bone marrow infiltration is less than before. Still, at 4%, the aspirate flow is the same as when I started Rituxan treatments in November of '09, so it's anyone's guess as to what we'll see a year from now.

Til then, I'll keep pushing the rock!

Merry Christmas to all and a Happy New Year too!

Restaging

2010-12-16T18:02:00.000-08:00

Monday was a busy morning for restaging at NIH:
        1) 17 vials of blood at 7 am
        2) 45 minutes in the MRI hotdog chamber at 8 am (sounded like I was surrounded by a swarm of helicopters)
        3) Ultrasound at 9 am.
        4) Bone Marrow Biopsy at 10 am.
        5) EKG at 11
        6) Back to work at 1

I should get my FACS results for the bone marrow aspirate and peripheral blood in a couple days. The good news is that ultrasound of my spleen shows that it now measures 10 cm. That's down from 13.4 cm at diagnosis, and means the overall volume at diagnosis was 2.4 times what it is now -- comparitively large although a spleen size of 13.4 cm isn't abnormal for a tall man. This bodes well for having delivered a fairly strong punch to the hairies.

The bone marrow biopsy was the most pain-free so far, but mine was still done by hand -- not the new bone marrow drill that gets the job done in just 10 seconds. NIH started using the drill recently, but they didn't have any bits left from the initial order, so I'll have to wait until next August (biopsy #7) to see if the drill is as fast and painless as claimed.

My CBC results were very good. The WBC is back up to 3.74, platelets are up to 139 and ANC is at 2.5. There is no sign of any fat in my liver and my AST and ALT are still great at 20 and 30, respectively.

We're assuming the FACS will be positive, so I'm scheduled for a clinic appointment next Wednesday and will start my second round of Rituxan on the 28th -- 8 cycles over 8 weeks. When I'm done this round, I'll have received 16 cycles of Rituxan over the course of 16 months.

I'll post my FACS results as soon as they come in.

I Want a New Drug ...

2010-11-20T16:59:00.000-08:00

I want a new drug...

Okay, maybe not yet, but it looks like there are lots of new potential candidates for treating HCL that still have yet to be explored. Two posts ago, I mentioned a new third-generation antibody that has the potential of being 5 to 100 times more powerful than Rituxan but hasn't been used to treat HCL yet. I'm hoping some preliminary in-vitro studies will be conducted soon.

Today, I found another one -- a Btk (Bruton's tyrosine kinase) Inhibitor, PCI-32765, that is currently in Phase I clinical trials in patients with B cell malignancies (specifically Non-Hodgkin's Lymphoma). Btk is an essential signalling factor needed for the development of B-cells. By inhibiting it, the Btk protein production is blocked and B-cells can't develop. The inspiration for developing the drug was born from a disease, XLA, in which B-cells are absent from the peripheral blood because Btk is not produced due to a Btk gene defect.

What's great about this drug is that it's a pill, taken orally, that inhibits Btk production and thus B-cell production. Since HCL is a B-cell malignancy, I've asked the Hairy Cell Consortium if they are familiar with the drug and whether it may be a candidate for a Phase 1 trial to treat relapsed and refractory HCL patients. I'll let you know if they respond.

"This is a very selective compound for B-cells, and it could represent an important alternative to rituximab therapy for the treatment of B-cell NHL. Other obvious applications include autoimmune disorders such as rheumatoid arthritis and lupus, and Pharmacyclics also has strong preclinical efficacy with PCI-32765 in these disease models," said Dr. Mark Genovese, Professor of Medicine and Co-Chief of the Division of Immunology and Rheumatology at Stanford University Medical Center and member of Pharmacyclics' Scientific Advisory Board. [Taken from Pharmacyclics Press Release dated April 13, 2009]

Wouldn't it be great if we HCL'ers could knock out minimal residual disease (MRD) and then take a pill as maintenance therapy so that we'd never have to worry about it ever coming back? Even better if it could act as the first-line therapy someday and eliminate the need for chemotherapy altogether (and side-effects like increased secondary cancer risk and impact to T-cell counts), or provide a new treatment alternative for patients with HCL-V (the variant form of HCL that doesn't respond as well to Cladribine).

Prediction?...Pain!

2010-11-11T17:47:00.000-08:00

After months of putting it off, I finally went to a new dentist last week. He told me to see another endodontist to get a second opinion about the root canal and fistula that never resolved after the retreat 18 months ago. The endodontist told me he's stymied, that it's not good to let the fistula linger because of possible bone damage, and to get the tooth (#14 molar) pulled. Since the tooth extends into my nasal cavity, they may have to sew in some new bone to make it heal faster. Once it heals, they'll install a post and a false tooth.

Oh, and my dentist found a cavity under a cracked filling.

The tooth extraction and filling cover the first week of December. The following week, Dr.K is going to restage my progress in case they need to retreat with another round of Rituxan, which means another bone marrow biopsy (#6) on the 13th.

My good friend Mr. T would like to have a few words:

Prediction? ... Pain!

The protocol has officially been ammended to allow two rounds of Rituxan for the delayed Rituxan cohort (the one that I'm in). It's a simple one-line addition: "Also may repeat for those with blood MRD six months after delayed Rituxan." My flow was negative at 6 months post-Rituxan but has now been positive for 3 months, and will likely still be positive when I restage, so I'll probably receive another 8 rounds of Rituxan starting in January. I'm very hopeful that this round may be even more effective than last year's since my counts are in good shape and my neutrophil level is much higher.

A high neutrophil count has been shown to correlate with improved antibody-dependent cell-mediated cytotoxicity (ADCC). In other words, the more neutrophils you have when you start Rituxan therapy, the more they can help kill the cells that are tagged with Rituxan. I'll be interested in seeing if I have another incidence of Rituxan-Related Late Onset Neutropenia (RRLON) at week 14 this time around.

I had a physical at my PCP on the 3rd. Everything checked out fine. My liver enzymes are holding steady at 22 for both the AST and ALT and my HDL is back up to 40 for the first time in 2 years! I received 3 vaccinations: tetanus, pneumonia, and flu. I couldn't move my left arm for 4 days, but now I feel great.

Aside from that, I've been dabbling in some new favorite hobbies: studying organic chemistry, molecular cell biology, genetics and bioinformatics so that I can better understand some of the papers I've been reading on antibody research and lipid rafts. I wish I could go back to school full time.
(12/2/2010) Tooth Extraction Follow-Up: Had the tooth pulled. Everything went fine, and the major bleeding stopped within minutes, although there was a very slow trickle afterward. I'm hoping this means that there is continued improvement in my platelet count. I was able to go without any gauze within 3 hours (probably sooner if I hadn't been so cautious). There were several cysts (about 1 to 1.5 mm) that had formed at each root tip and had to be rigorously scraped off the bone after the roots were extracted. The worst part was the high pitched squeal of the drill used to segment the root sections so they could be pulled individually. 1 day later, everything feels fine. I just need to eat soft foods and avoid that side of my mouth for a few days. In 2 to 3 months, I'll have an exam to verify the bone has grown back and then get a post installed.

A New Hope

2010-10-11T19:39:00.000-07:00

Good news! The latest FACS results from blood taken on September 30th indicate no change in the peripheral blood hairy cell burden or the percentage of lymphocytes that express the hairy cell phenotype (characteristics). This gives more credence to the hypothesis that the positive FACS results are due to the Rituxan monoclonal antibodies (mAbs) detaching from the residual hairy cells and clearing my system. The hairy cells may have always been there, but now they are no longer masked by the Rituxan and are once again detectable by FACS. The important point is that the percentage of hairy cells in the blood remained unchanged at .04%, so the malignancy is not dividing/growing in numbers. We'll continue to monitor over the months to come, but given that the results are identical to those from 4 weeks ago, I'm very hopeful.

Here's a video of my latest bloodcounts. Please excuse the melodramatic soundtrack, I was just indulging in some creative publishing ...
In other news, I'm very excited about a drug I found while researching the relationship between lipid rafts and anti-CD20 monoclonal antibodies. It may have significant potential in treating HCL -- perhaps 5 to 100 times greater potency than Rituxan. Pursuant to my inquiries, HCL investigators, who were previously unaware that the drug existed, are now performing detailed analysis of its potential in treating HCL that could lead to some preliminary in vitro laboratory studies. If all goes well, it may be used in a Phase 1 trial to treat HCL patients who otherwise would have to resort to palliative treatment options. Maybe several years down the road, it will also become part of the standard arsenal in treating this disease.

We HCL'ers are fortunate to have so many options and doctors who are willing to listen to and pursue our questions. It's a good feeling to know that in some small way we can help fight the war on cancer and not be its victims.

Double Trouble

2010-09-07T19:02:00.000-07:00

The tumor load in my peripheral bloodstream doubled over the past 3 weeks. I had a FACS done on August 31st, and the report indicated the percentage of hairy cells increased to .04% from .02%. If the cells are really doubling every three weeks, then I'll have an appreciable burden (around 1%) by January. Currently, about 5% of my lymphocytes are hairy cells. I just got the flow results today and haven't talked to Dr. K yet about what it all means. Still, I've asked to have another flow on Sept. 21st. If the burden doubles yet again, then I'd like to get another bone marrow biopsy in early October to see if the cells are back in the core.

On the bright side, my counts are continuing to improve, so at least the hairy burden is currently low enough so as not to significantly impair my marrow function. My WBC is at 4.03, my neutrophils are at 2.6 and my platelets are at 141 -- an all time high since treatment. I'm still hopeful that I might be able to get another Rituxan treatment while the overall burden and clump sizes are low.

I've read some interesting articles on leukemia using fat as fuel as well as fatty acid involvement in hairy cell membrane morphology. A study demonstrated how drugs that inhibit fatty acid oxidation may sensitize leukemic cells to drugs that induce apoptosis. I'm very interested in finding out whether there is a relationship between fatty acid oxidation, body mass index (BMI) and the effectivity of Cladribine. If one could show that people with lower BMI respond better to Cladribine chemotherapy, then perhaps general approaches to reducing BMI prior to treatment with 2CDA could result in better outcomes for all patients. My crazy brain at work. (Afternote: Turns out there is a basis for my query regarding a correlation between BMI and chemotherapy, although it's not directly related to HCL. A study of childhood leukemia patients showed that patients with high BMIs were less likely to respond to chemotherapy. While the theory reported is that cancer cells sequester in body fat, I have my feelings that cellular membrane factors may be involved as well.)

Time to go exercise...

(More random thoughts, 9/9/10) I've been reading about cellular plasma membrane structures called "lipid rafts." Although these structures are readily observed in cultured cells, they have not been observed in live cells, and their existence in live cells is considered controversial; however, I wonder if hairy cell filopodia (aka villi -- the fine hair-like projections of hairy cells) are actually extrusions of cytoplasmic material from lipid rafts which have large cholesterol concentrations (remember -- hairy cells have high cholesterol content). I read an abstract from a study entitled "Lipid Raft Disruption Prevents Apoptosis Induced by Cladribine." It indicates that although leukemic test cells completely absorb Cladribine, disrupting the lipid rafts inhibited the flow of calcium ions through the plasma membrane and reduced the apoptotic effects of Cladribine. Although the study used ALL cells, I wonder if this is a reason why Cladribine doesn't work well for some HCL patients (the lipid rafts are disrupted or vary in some way that prevents proper biochemical flow to induce apoptosis). Still, the study probably used cultured cells, so it's hard to know if it applies to live cells. I'd like to get the full article and learn more about the causes of lipid raft disruption to find out if there are things that can be done to make Cladribine more effective for all patients. Who knows, maybe this is a factor in HCL-V, and figuring out a way to open the ion pathways will make Cladribine effective in that variant of the disease too.

Similarly, treatment with interferon-alpha has been shown to reduce HCL cholesterol content and villi length. This would support my theory since lipid rafts are assumed to contain large amounts of cholesterol. Reducing the cholesterol content of the lipid raft would reduce its area and correspondingly, the amount of material extruded to form the villi would be reduced -- resulting in shorter villi. I don't know why I write this stuff. Aside from the fact that I'm desperate to kill these hairy bastards, I suppose I'm hoping a grad student will take it on as a project or at least comment on its plausibility.

(Even more random thoughts, 9/10/2010) This is kind of cool. I just found an abstract for a study entitled "Microvilli structures on B lymphocytes: inducible functional domains", which states: "We also discovered that depletion of cholesterol, using b-methyl-cyclodextrin, lowered the number of microvilli, indicating that intact lipid rafts are required for their expression." This applies to the microvilli of normal cells, but it is in keeping with my hypothesis regarding unusually large lipid rafts as the source of the filopodia (aka villi of hairy cells. Perhaps my hypothesis is right. Now if only I could win the lottery and fund my own studies...

Interestingly enough, there is a patent for a formulation of Cladribine that uses b-cyclodextrin as the soluble agent in lieu of the original benzyl alcohol and propylene glycol cosolvent soluble agent combination. This is a similar compound as that referred to in the paragraph above (Both β-cyclodextrin and Methyl-β-cyclodextrin (MβCD) remove cholesterol from cultured cells) and it's used to deplete cholesterol and reduce the number of microvilli on B lymphocytes. If hairy cell villi are indicative of lipid rafts, and lipid rafts are necessary to allow ion flow and induce apoptosis, then perhaps this formulation of Cladribine is slightly less effective than the original version. I'd like to know which version of the drug I was given. If b-methyl-cyclodextrin acts as a lipid raft disrupter, then maybe the original formulation is more effective in patients with variant lipid raft function.

(9/11/2010) I found another great article: "CD20-mediated apoptosis: signalling through lipid rafts," which seems to imply that in order for Rituxan to induce apoptosis, it must cross-link CD20 proteins that are located in separate lipid rafts. My initial thought was "does this mean that if your cells have fewer rafts or if the rafts are too large, the drug will be less effective?" and this thought turned out to be mirrored in the final thoughts of the study report: "Finally, it will be important to test the prediction that the size or abundance of lipid rafts in B-cell membranes is a contributing factor to the susceptibility or resistance of patients to CD20-mediated B-cell depletion." This study's findings resonate a common theme with the other studies I've referenced regarding the involvement of lipid rafts in apoptosis.

Much of this report seems to read as if the high cholesterol content of the cells is necessary in order to allow the calcium ion flow needed for apoptosis to work properly. This would indicate that going on a low-cholesterol diet during therapy to try to starve the hairies may be counter-productive. Since the underlying apoptotic biochemical process seems to be the same for Cladribine induced apoptosis as it is for anti-CD20 induced apoptosis, maybe cholesterol gets synthesized into other chemicals during apoptosis -- causing the hairies to suck in more cholesterol from the peripheral blood as they try to survive. Maybe this explains why my blood cholesterol dropped precipitously during Cladribine chemotherapy (HDL went from 30 to 18 in a matter of days, LDL went from 90s to high 60s). I'm guessing that partial apoptosis biochemical processes started and consumed cholesterol, but the calcium mobilization was inhibited so as the cells survived, they consumed more cholesterol from my peripheral blood to reconstitute themselves. Ultimately, many of them died after six months (went from 80% bone marrow infiltration at 1 month post chemo to 30% at 6 months) probably due to DNA damage and slow but sure calcium mobilization, but too many survived.

I found another article which reinforces and provides further detail on the involvement of cholesterol in B-cell apoptosis: "Cholesterol depletion inhibits src family kinase-dependent calcium mobilization and apoptosis induced by Rituximab crosslinking."

Hmmm....does this mean I should eat Ben and Jerry's Vanilla ice cream during therapy?  Of course not, fat and cholesterol are different substances. Maybe shrimp is a good compromise -- low in fat, but high in cholesterol. Leukemia is so paradoxical to the conventional mindset. This is interesting because studies in many solid tumors (like prostate cancer) show that cholesterol depletion aids in apoptosis. The differences between leukemia and solid tumors are fascinating. Time to go watch Woody Allen's "Sleeper" -- turns out chocolate cake is good for you after all...

(9/18/2010) I got a great reply from the "Hairy Cell Consortium" regarding some questions I had regarding lipid raft research for HCL:

My e-mail to them read as follows:
      Given the findings of the following studies:
          "CD20-mediated apoptosis: signalling through lipid rafts"
          http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1782791/pdf/imm0107-0176.pdf

          and

         "Lipid raft disruption prevents apoptosis induced by Cladribine"
          http://www.ncbi.nlm.nih.gov/pubmed/16730061

          isn't it possible that lipid raft disruption may play a
          significant role in why these drugs
          are are not effective for some patients?
          Why isn't there more research to characterize
          HCL lipid rafts and determine the role that lipid
          rafts have in the disease?

Here's their reply:

         Dear Mr. Howard:


         The question that you pose about the potential
         importance of "lipid rafts" and response to therapy
         in hairy cell leukemia is excellent. To our knowledge,
         the characterization of "lipid rafts" in hairy cell
         leukemia has not been published. In contrast, lipid
         rafts have been explored in chronic lymphocytic leukemia
         by several investigators. The presence of lipid rafts has
         been correlated with response to cladribine as well
         as response to monoclonal antibodies in vitro. The
         monoclonal antibodies that have been studied include
         both Rituximab and Alemtuzumab. Since both of these
         agents may have some benefit in this disease, all patients
         have not responded. It would be interesting to
         correlate the responsiveness to these agents as well
         as to the purine nucleoside analogues. This is the type
         of study that might be conducted within the Hairy Cell
         Leukemia Consortium. Your question has merit
         because it might provide predictive biomarkers to
         determine who will and will not respond to these agents.

       Regards,
       The HCL Consortium Team

This response made me very happy. Hopefully, they'll perform some studies. Who knows, maybe the research will not only provide predictive biomarkers but ways to tailor the structure of antibodies to conform to variances in lipid raft size and placement that fall outside the range accomodated by the current antibodies' structures.

The FACS of Life

2010-08-20T20:25:00.000-07:00

You knew it was only a matter of time before I had to use that corny title for a blogpost, but bear with me, it follows a coherent theme.

Other candidate titles for this post included:
   Dirty Hairy
   From Hairy to Eternity
   The Good, The Bad, and The Hairy
   Gone Today, Hairy Tomorrow
   The Cells that Wouldn't Die
   Protocol
   and Hair We Go Again

Simply put: you take the good, you take the bad, you take 'em both and there you have the FACS of life...

The Good: The Rituxan treatments worked really well and as I wrote in my last post, the hairy cell burden in my May bone marrow biopsy was zero (although the bone marrow aspirate [liquid] showed 2.1% hairies). Likewise, I just had a complete blood count last week and my counts are at historical highs since diagnosis, so my marrow is continuing to rebound and keep me healthy.

The Bad: My FACS results from last week showed some hairies in the peripheral bloodstream (.02% of the peripheral blood monoclonal cells), but there are several reasons for why that may be.

The Theories:
   #1: It's very possible that the few hairies which were bound with Rituxan but not completely killed via apoptosis or immune system attack, were undetectable in prior FACS tests due to the effects of the Rituxan covering the surface. Now that the Rituxan is flushing out of my system and coming unbound from the hairies, those cells are once again detectable.
   #2: The cancer that wasn't killed by the Rituxan (some of the cells in the aspirate) are starting to proliferate again and seep into my peripheral bloodstream.

The analysis:
   Usually the simple answer is the correct one (unfortunately #2 is the simplest), but we are sailing in uncharted territory right now, and there is plenty of time to perform more tests over the coming months and really get a feel for what is going on. Theory #1 is highly optimistic but still plausible, and it's still very possible that as my marrow rebuilds, my immune system will either keep the remaining HCL in-check or attack and destroy it. Time will tell.

What's next:
   Given how well Rituxan worked the first time considering my HCL burden after Cladribine chemotherapy was still substantial, I believe I would benefit from a second round of Rituxan treatments if they are offered to me. The possibility of adapting the protocol accordingly for my cohort is being considered (the simultaneous chemo/Rituxan cohort is allowed two rounds of Rituxan, but my delayed Rituxan cohort is currently allowed only one).
   In the meantime, I'm interested in seeing how my body will respond to the remaining hairies and feel that doing some more FACS tests to see if the burden increases or becomes undetectable again will help to substantiate or disprove theory #1. Over the next few months, we'll run some more FACS tests and see what happens. Let's hope my immune system kicks it.

Here's a slide show of my latest blood count results:

Since my last post in May, I've really been enjoying life. Taking lots of time to be with the family, a trip up to Hershey Park, and enjoying the weekends when the heat or rain doesn't make that impossible. It's been an incredibly happy time and given that the blood counts are continuing to improve, I really don't care about the few cells that were found in the peripheral bloodstream.

I should have another FACS in 4 to 6 weeks. I'll let you know how it goes.

Moving the Rock.

2010-05-18T12:02:00.000-07:00

The rock has moved!

I received my bone marrow biopsy results yesterday. They read as follows: "No morphologic or immunohistologic evidence of residual hairy cell leukemia." In other words, negative for hairy cell. You may recall that the bone marrow infiltration in late October was still 30% six months after Cladribine chemotherapy treatment, just before receiving Rituxan. The NIH Clinical Trial for new patients combining Cladribine and Rituxan has done a great job! Excellent news to end one of the most awesome weeks of my life.

The only thing that can put a bigger smile on my face is this:

My daughters

My peripheral blood FACS was also negative for HCL. The FACS for the bone marrow aspirate is still positive for HCL (dropped from 4% in late October to 2.1% last week), but the CD20 absolute binding tests show a dramatic decrease in the binding capacity (dropped from a capacity of 80,000 molecules of Rituxan to 8000) because a large amount of Rituxan is now already bound to the existing CD20 proteins on the cells now that I've received Rituxan treatments. This means it may still be working. CD20 proteins are overexpressed on the outside of the hairy cells, and Rituxan binds to those proteins then kills the hairy cells. A significant amount of the cells may continue to die over the next six months, and there is a possibility that the bone marrow aspirate will also test negative six months from now.

I am now in complete remission !!!

New Arrival!!!

2010-05-13T14:34:00.000-07:00

I'm proud to announce the arrival of our second child.
She arrived today, 5/13/2010

Weight: 9 lbs, 8.3 oz.
Height: 21"
Ingredients: lots and lots of sugar, spice and everything nice.

Baby, Mommy, Daddy and her big sister are all happy and healthy!!!

Our new baby girl!

Benefits of NIH HCL Trial Participation

2010-05-10T17:51:00.000-07:00

I've read a lot of bulletin board posts with various insights regarding participation in the NIH Trial for Newly Diagnosed HCL Patients so since I'm participating in the trial, I thought I'd offer my own.

While I have the advantage of living close to NIH, I've been in touch with many patients who have had to deal with the logistics of participating in the trial from all over the country. Here are many of the trades people make when considering trial participation:

Trade #1: Can I afford to travel to or stay at NIH for 8 weeks of Rituxan treatments?
   Fact: You don't have to. Rituxan can be administered by your local doctor. You only need to travel/stay at NIH for the first week of chemotherapy treatment. NIH will send the Rituxan to your local doctor and coordinate the administration free of charge.

Trade #2: My local oncologist can provide the Cladribine and Rituxan combination, so there's no need to participate in the trial.
   Fact: While local administration of the Cladribine/Rituxan combination is becoming more common, most insurance will only cover the cost of 4 weeks of Rituxan. By participating in the NIH trial, you'll receive up to 16 weeks (2 cycles at least 6 months apart with 8 weekly rounds per cycle) of Rituxan free of charge. Most insurance companies view the free NIH-provided Rituxan and expected increase in remission as a major cost-savings and will cover the entire cost of local Rituxan administration (local Dr. time and facilities costs).  Since Rituxan effectivity is dependent on the size/radius of the remaining clumps of hairies, long-lasting remission and eradication is much more likely with 8 cycles per treatment than with 4.  Independent adminstration of Rituxan without monitoring minimal residual disease (MRD) in a clinical trial setting does not provide an effective means of treating the disease. Once the trial is completed, local oncologists will be provided with the most effective combination therapy treatment.

Trade #3: The trial doesn't provide any major advantage.
   Fact: Prior trials in Italy combining Rituxan and Cladribine resulted in a significant increase in complete remissions and elimination of minimal residual disease (MRD). It is believed that this may increase the duration of remission, which is being studied by the NIH trial. The NIH hyper-sensitive MRD test is able to detect 1 hairy in 1 million mononuclear cells -- 100 times more sensitive than a standard FACS. This is a significant advantage -- allowing Rituxan to be administered at a point when it will be most effective. This also means that Rituxan will only be administered if it is necessary. Only NIH can perform this test!
   Whereas most doctors aren't proactive in following their patients and wait until blood counts indicate the need for re-treatment, Dr. Kreitman will actively study your progress and treat the earliest signs of MRD, which may possibly increase the duration of your remission (one of the hypothetical effects being studied).

Trade #4: There are risks associated with Rituxan. Cladribine is highly effective in most patients, so I'll do that for now and only take Rituxan later if it becomes necessary.
   Fact:  Data indicate that 40% of patients relapse after only 10 years of single-drug chemotherapy. To prevent significant bone marrow suppression, it's desired to limit a patient to two treatments of purine analogue chemotherapy (Cladribine or Pentostatin).  The prevailing theory is that Rituxan is most effective when used in conjunction with a purine analogue so that the clumps of hairies are unclumped/diffused prior to administering it (being studied by the trial). This allows Rituxan to destroy the individual hairy cells immediately instead of slowly peeling the outer layers of the hairy clumps (resulting in a direct additive effect vs. a percentage of the remaining load). Don't lose this advantage by deferring Rituxan treatments until after chemotherapy is no longer viable. One look at my ANC plots (see prior posts), and you can see I owe my overall strong response to the Cladribine/Rituxan combination.

Trade #5: I can't afford to travel to NIH.
   Fact: A lot first-time patients deal with the cost/benefit trade-off of travel to NIH, and rightly so.  Once accepted into the trial, NIH will cover the costs of all subsequent travel for the patient (spouses and children are not covered).  Angel Flight and the Air Charity Network offer flights to patients in financial need.

Trade #6: I can't afford accommodations while at NIH.
   Once admitted to the trial, NIH will provide free accommodations through their in-patient hospital. While qualifying for the trial, you may need to spend two nights at a local hotel. Current rates for the Bethesda Marriott are approximately $139/night. You'll find that the current commercial rates are often better than the NIH negotiated rates, so ask for both.

The best way to make a fully informed decision is to gather as much information as possible. Dr. Kreitman is always available and will quickly respond to your questions. Email him at kreitmar@mail.nih.gov.

.

Turbulence

2010-04-10T07:36:00.000-07:00

The approach for my soft landing has been suddenly interrupted by some unexpected turbulence. I had a CBC and FACS performed on Monday. For the most part, my counts were good, but as shown in the plot below, the one exception was a doozy -- my absolute neutrophil count dropped dramatically from 1.97 two weeks ago to .81 on Monday. This sudden drop definitely had me concerned, but to my relief the other counts are still good -- the lymphocyte level remained steady, my platelets increased slightly and my liver enzyme levels are now well within the normal range.

My FACS results came in on Thursday and were still negative -- no detectable hairies in the peripheral bloodstream. Everything else is good, but the neutrophils have dropped suddenly about 14 weeks after my last Rituxan treatment (12/28/09). What's going on? The initial direction from Dr. K is to wait until my marrow biopsy on May 10th to evaluate the marrow function, but after some more investigation, my best guess is that I've experienced a side-effect of Rituxan known as Rituxan related late onset neutropenia (RRLON).

A cursory evaluation of the available research papers on RRLON indicates that in a lymphoma study in which patients were treated with both chemo and Rituxan, 23 of 107 patients experienced some form of RRLON. The typical median ANC nadir point was .61, and required 4 weeks to recover. I've asked Dr. K for his opinion and a response is pending. In my opinion, another CBC by next Wednesday would make sense to quantify the nadir and determine whether I'm still on the downturn or moving toward recovery.

I'll keep you posted.
BTW: here's an interesting article regarding the health care debate ;)

Update:
Just had another CBC today (4/29) per my request, and the news is good! The late-onset neutropenia (LON) has resolved and all my counts are in great shape (except the platelets). I'm very confident that this was a Rituxan-related event and pleased that my neutrophil level is now well within the normal range. As you can see in the ANC plot below, the neutrophil level is almost close to the peak level since I've started collecting CBC data. Even better, my WBC is the highest it's been in years considering that prior to treatment a large percentage of the WBC consisted of hairy cells. I'm very happy!!!

Soft Landing

2010-03-23T17:42:00.000-07:00

I just had another complete blood count (CBC) on Monday and things look like they're stabilizing. The platelets are still low but within a normal range for remission and since they're stable, I'm happy. I was hoping the neutrophils would increase, but they're still in a normal range although they went down slightly over the past month. As you can see in the plots below, my counts have pretty much come in for a soft landing, and stability in the normal range is a good thing.

Following up on the liver enzymes: they're slightly back up over the normal limits, so I don't think the chamomile tea was a major contributor. I ate some foods with wheat and walnut ingredients a few days before the test (birthday and wedding celebrations), so that may have something to do with it. A fatty liver can cause gluten intolerance and low platelets due to decreased production of thrombopoietin, so I may still be fighting some fatty liver issues.

The weather last weekend was great! I got out and rode my bike 22 miles on the C&O Canal on Sunday. I'm anxious to push for 40 next weekend!

A Hairy Update

2010-03-14T09:30:00.000-07:00

The past two months have been great! The February snowpocalypse gave me an opportunity to test my stamina shoveling and snowblowing, and I felt great afterward. I even shoveled out my neighbor's driveway. My FACS tests continue to show 0% hairy cells in the peripheral blood stream, and I'm still waiting for my next bone marrow biopsy in April to see if all evidence of hairies in the marrow has disappeared. I think it has. The Rituxan after the chemo really did the trick.

I continue to limit gluten in my diet and have stopped drinking herbal tea (specifically chamomile). Correspondingly, my liver enzyme levels returned to normal on my last blood test in February. I'm very interested in seeing if they continue to stay down when I go back in on the 22nd, now that I've stopped the tea. Interestingly, my platelets and neutrophils also came down a bit after stopping the chamomile, which is anecdotally tied to increasing neutrophils, but all my counts are still in the normal range.

I'm anxious to start riding my bike along the C&O canal again. Yesterday, I rode 20 miles in an hour using the "Pike's peak" profile at the maximum resistance level on my exercise bike. I would never have been able to do that level of resistance at any time before in my life. I really think I had HCL (and some other issues) "in-check" and undiagnosed for a long time before being diagnosed. I'm anxious to get outside and see what I can do now that it's warming up.

Life is definitely more normal now, although I'm not sure that's necessarily good. I spend a lot less time researching HCL. Still, I try to keep up with the latest news. For those who are interested, here's a link to a hairy cell video lecture by Dr. Kreitman, "Updates on Therapies for Hairy Cell Leukemia", on the current state-of-the-art of HCL research.

We had a 4D sonogram of baby girl #2 on the 7th (Cladribine did not reduce my fertility and may have improved it by eliminating the effects of chronic leukemia). She was very shy and wanted to bury her head from view but we got several good peeks, and she looks a lot like her big sister. We're very excited to meet her in person in May.

Next Friday, the 19th, is my birthday and coincidentally the day my sister Elena is getting married. It'll be a great celebration with the family, and Claire is excited to be a flower girl with her cousin Olive. The next day, Saturday the 20th, marks 1 year since my diagnosis. I'm grateful to be celebrating it.

My latest labs look good. I'm going back in on the 22nd for another set, so I'll probably update the charts and publish them here when I get that data.

It is a Happy New Year!

2010-01-04T18:44:00.000-08:00

My 8th and final Rituxan treatment was last Monday, December 28th, and it feels great to be done. I'm in great shape now, and the Holidays were wonderful. I got to spend lots of time with Claire, who never ceases to amaze me. She'll be 2 this Saturday, speaks in full sentences and loves to keep us entertained by saying such phrases as "Hey, can I have more French Fries please, lady?" to the waitress at Outback Steakhouse, calling us with the redial button from Grandmas without permission, putting her bib on and walking into the kitchen to say "Grandma, I'm hungry", and saying things like "I don't have time to talk right now" and "I love you too, truly" when she pretends to call people on the phone. We also found out that baby #2 is going to be a girl. We're favoring naming her Grace (more like Amazing Grace). If she's anything like Claire, we're going to have our hands full in 4 months...

So far 2010 has been a good year, but I guess 4 days isn't much to go by. Still, the results of my last blood test were great, and that makes me optimistic. I don't look back on 2009 with disdain,I met too many awesome and wonderful people -- patients, doctors, and nurses, and I re-established bonds with friends and family. Isn't Facebook awesome? (ha ha). Likewise, I learned a lot, grew alot and lived a lot. I'm grateful to be doing so well at this point, and thankful for all the prayers and thoughts caring people like you have sent me.

Now, back to the blood. All the reds are back in the normal range (not just by remission standards -- we're talking normal normal). Likewise, my white count is strong and the neutrophils are awesome -- well into the normal range. Most of the remaining lymphocytes are T-cells and NK cells at this point, the B-cells having been wiped out for the most part. I'm hoping the latest FACS (from the post-treatment sample drawn today) will detail those levels, but it won't be ready until next week.

Here are my latest plots. Check out the massive increase in the neutrophils over the past two weeks. The Rituxan really went to town and helped me turn a marginal response to Cladribine into a complete, and what I believe will be a lasting, remission!

Happy New Year!

Wipe Out!

2009-12-22T16:51:00.000-08:00

The Rituxan treatments have been an overwhelming success!

While I haven't taken the time to write a worthwhile update on my current status, I'd like to share with you the flow results from blood taken prior to the Week 5 treament. The flow was negative -- no hairy cells could be detected using the standard FACS, which is sensitive enough to detect 1 hairy in 10,000 mononuclear cells.

The Cladribine/Rituxan one-two punch worked and was the perfect combination of what I needed. I'm very relieved and very grateful to have found Dr. K's trial. I've now completed 7 of the 8 weekly Rituxan treatments. The last treatment went very well and didn't require Tylenol or Benadryl pre-meds (to eliminate undue strain on my liver).

A week prior, the treating nurse gave me my Tylenol pre-meds half an hour before drawing my blood for the chem20 tests, which include my liver enzyme levels. Not surprisingly, both the AST and ALT enzyme levels were about as high as I'd seen in awhile. This week, the AST was back to normal and the ALT was 50% higher than normal, which isn't too bad for me. I had a consult with a hepatologist, who wasn't surprised that in general my enzymes were elevated. It is not uncommon in half of all cancer patients, given the stress of chemotherapy and all the other agents the body is exposed to. I don't know if that generalization applies to Cladribine chemotherapy specifically, but it helped me feel better about my roller coaster enzyme levels.

Based on prior imaging tests, it appears that my liver is somewhat fatty, and the hepatologist seems confident that a better diet and more exercise will likely return the liver to normal. I'll continue to persist at maintaining dietary and physical discipline in hopes that the fatty condition of the liver can be reversed. They are running additional tests, but right now, it looks like I'm just paying the price for prior years' poor diet and some genetic pre-dispositions.

Git 'r Dun

2009-12-07T08:23:00.000-08:00

Really good news this week!

My neutrophils jumped from 1.29 last week all the way up to 1.70, and my liver enzymes dropped by more than 10%. The AST level is back to normal. Everything seems to be moving in the right direction, so I think I'll stick with the vitamin and chamomille cocktail I described in my previous post. I'm still doing the coffee/caffeine thing too.

As I write this post, I'm getting my 5th infusion of Rituxan. Prior to treatment, they drew blood for a FACS analysis to count the peripheral hairies, but I'm very confident they won't find any this time.

I'll add plots of the last 3 weeks' blood counts tonight, when I can get to a computer.

Here they are. As you can see most of the counts are back up to the levels they were at just prior to my first Rituxan treatment, when they had already peaked and had started to trend downward. Let's hope the upward momentum keeps going.

Boring is Good

2009-11-30T11:56:00.000-08:00

Just finished my 4th cycle of Rituxan (gen. Rituximab), and it was extremely uneventful. Good thing too because I didn't take any Benadryl pre-meds this time. Infusion time was almost exactly three hours. This allowed me to stay alert, do some work on my iPhone, and now I'm about to go back to work at the office. Hopefully I can get 5 hours in before the day is done.

Basic dose information for me is as follows:
Total Dose: 803 mg
Concentration: 2 mg/mL
Dose Rate: initially at 50 mL/hr (100 mg/hr) increasing by 50 mL/hr every 15-30 minutes to 200 mL/hr (400 mg/hr).

The Rituxan total dose is calculated as follows:

My counts are pretty much holding steady for now, in a good range but not yet back up to remission levels. My liver enzymes crept up another 10 to 20%. It seems like nothing I do to make them better seems to work. I've read that people with Crohn's disease secrete high levels of TNFa and that TNFa is also a bone marrow suppressant. Perhaps other digestive issues such as gluten intolerance and Celiac also contribute to high TNFa levels independent of the presence of HCL. If so, then perhaps eliminating chamomile, vitamin A, vitamin E and Omega supplements in hopes of improving my liver function panel actually increased my residual TNFa levels and thus my liver enzymes too (the opposite effect of what I wanted). Then again, perhaps I'm just too impatient and overanalyze without enough data. I've asked for a cytokine panel, or at least a TNFa measurement, but have not heard back yet.

This week, I'm to going to take a vitamin D (1000 iu), E (200 iu) and an Omega-3-6-9 supplement twice daily (total 2000, 400 and 2) and drink chamomile three times a day to suppress TNFa and see if my counts go from holding steady to a pronounced improvement. I'll also take a daily multivitamin in the morning.

Overall it was a boring day, and boring is good.

The Vanishing Point

2009-11-24T14:40:00.000-08:00

All I can say is Wow!

After one treatment with Rituxan, FACS results indicate that the percentage of hairy cells in my peripheral bloodstream plummeted from .4% to .05% -- a reduction of 87.5%! I can only hope that it's having the same effect on my marrow infiltration, but I believe it is.

I've now had 3 treatments with Rituxan, so one can expect that the percentage of hairies has now reduced to undectable levels with the standard FACS MRD detection technique. Blood for the next FACS will be taken prior to the Week 5 treatment, so we should know those results in about 3 weeks. It's likely the malignancy will be undetectable!

I also had my Pentamadine (lung antibiotic) treatment yesterday, and it went very well too. The taste was slightly bitter but tolerable. The Pentamadine is a nebulized once monthly treatment in lieu of Bactrim, to prevent the possibility of respiratory infection while being treated.

I'm still trying to figure out why my liver enzymes are elevated. I've been off Bactrim for 10 days, but my last chem20 panel indicated that both the AST and ALT liver enzyme levels went up slightly. I avoid all pain-killers except when they're required for my treatment. Gluten intolerance is also associated with tinnitus and elevated liver enzymes. I think the next step is to go strictly 100% gluten free -- pretty much live off fresh vegetables and meat all cooked at home for two weeks and see if the levels drop significantly.

Anyway, the good news is that the Rituxan is working very well. The FACS count after cycle 1 was .35 cells/uL. Assuming there are 6 liters of peripheral blood, this translates to approximately 2.1 million circulating hairy cells. This means the total HCL count went from 24 million down to 2.1 million in just 1 week.

If the kill process is arithmetic, and the kill capacity per cycle is only dependent on the available volume of Rituxan, then the second cycle may have already killed off the remaining circulating hairy cells; but if the reduction rate continues at 87% of the remaining cells per cycle, I'll still have a few circulating cells left in the near term after cycle 8 (the final cycle). As the cumulative concentration of Rituxan in my system continues its hairy cell search and destroy mission in the months that follow, the remaining cells should be annihilated.

Otherwise, if each round is only half as effective as the previous round, then the total peripheral load would be reduced by 95% in the short term after round 8, which is still really good, but may leave 10 to 20 thousand hairies remaining in the peripheral blood and possibly a hundred thousand or so in the marrow. That's why I need the hyper-sensitive MRD test.

Here's a semilog plot of the FACS cell count per micro-liter since I was diagnosed. If my estimates are correct, then at it's peak, I had 471 million circulating hairies. Now they're getting hard to count.

The treatments are going well. Let's hope all the cycles are as effective as the first one was!

I've got a lot to be thankful for this Thanksgiving!

Three down, five to go...

Rituxan, Week 2 -- Chimeric Boogaloo

2009-11-17T16:23:00.001-08:00

I had my second cycle of Rituxan yesterday, and it went very well. I arrived at the NIH/NCI day hospital at 8 am, was lined up by 8:30, did the blood letting thing soon thereafter and had my Benadryl/Tylenol cocktail around 9:30 or so. We waited for the CBC results before starting my treatment at 10 am. It went very quickly, and since my body is now adjusted to Rituxan, I didn't need any Demerol this time. We started out at a rate of 50, then cranked it up to 200 half an hour later once my vitals checked out okay. I was done in 2 hours 45 minutes. A lot faster than the 7.5 hours it took the week before!

I got the pre-treatment CBC results before leaving and was very surprised by how quickly (and high) my platelets had rebounded. When I left 6 days earlier, my platelet count was at 88, but it jumped up to 122 by Monday morning. As you can see in the plot, that's the highest they've been since late May.

All the other counts had also risen significantly to near pre-Rituxan treatment levels. Two down, six to go...

11/18/2009 Update: Just got my pre-Rituxan flow report for the peripheral bloodstream. It indicates that the concentration of hairies in the peripheral bloodstream doubled to .4% from .2% just 1 week prior. Likewise, the count per microLiter also doubled, so the increase was consistent from both percentage and count perspectives. Given the decrease in normal counts that were also observed in the CBCs since remission was suggested, it's likely that my remission was going to just last a few months, if that. Looks like we hit the Rituxan just in time!

Of Mice and Men ...

2009-11-11T18:27:00.000-08:00

I started Rituxan biotherapy on Monday in accordance with the NIH protocol. Rituxan is a chimeric monoclonal antibody. The Rituxan chimera is a hybrid of antibodies from both human and murine (mouse) antibodies. The CD20 antigen (a unique protein found on B-cells and abundantly on HCL mutant B-cells) is injected into a mouse, encouraging the production of antibodies. Antibody producing cells are then isolated from the spleen of the animal. These are then combined with immortal cells called myeloma cells. This results in a cell line that will go on producing the antibody indefinitely. Further genetic engineering removes the elements of the mouse cell that would normally produce an immune (allergic) reaction if injected into a human.

One of the forms describing the treatment actually said not to receive it if you have reactions to mouse proteins. How would anybody know that? Although there was that time I had rat-on-a-stick at the 1988 Seoul Olympics...

This is the 6-month post-chemo biotherapy to treat minimal residual disease (MRD). I was fortunate in that my tumor burden is very low, so not a lot of tumor lysis and subsequent reaction was to be expected; hence, less reaction than those with higher burdens in the peripheral blood and marrow. The percentage of hairies in my flow cytometry tests are .2% peripheral and 4% marrow (fairly minscule compared to people who rely on Rituxan as a first line treatment because they don't respond to Cladribine).

I was admitted as an in-patient on Sunday and treatment started on Monday morning. About 7:30 am, a phlebotomist came up to my room and drew blood for the pre-treatment CBC, chem20 and several other tests. Later in the morning, my IV line was placed. Even though I have good veins, they put an order in with the procedures unit to place my IV line using ultrasound. The nurse put the gel on my arm, swiped my arm, picked a vein and placed the line in under a minute. She was able to see the position of the catheter the entire time, so I didn't have to worry about it running into the side of a vein wall or valve. Nice!

My nurse, who was great, reviewed the purpose of the drug and possible side effects, the most common of which are chills, shakes and fever. Pre-meds included Benadryl and Tylenol and the initial Rituxan dosage rate was very low. The going in plan was 12.5 units (can't recall the precise unit label) steady for the first 4 hours, up it to 25 units at hour 4, then increase by 25 units every half hour after that unless reactions were seen. I was great the first hour, then I started to feel mild chills. I tried to fight it, but once I curled up under a blanket, I gave myself away and my nurse decided it was time to give me Demerol after a mild scolding for not telling her sooner. Demerol's a wonder narcotic for knocking out chills (among other things). I was fine after 15 minutes and after that, things went really well.

I took another Benadryl/Tylenol cocktail at hour 4. 10 minutes after each dosage increase, my temperature would go up (max'd at 38.6 C) but it would settle back down to the 37 to 37.5 range before the next increase. Vitals were taken every half hour prior to the dosage increases. Blood pressure was generally in the 118/69 range, pulse was normal and oxygen was anywhere from 95% to 98%. I finished the treatment in 7.5 hours.

I highly recommend that anyone receiving Rituxan biotherapy for HCL discuss Demerol as a option with their doctors. I think I would have suffered a lot without it and think it may help a lot of people who've generally just been treated with high doses of Benadryl. Dr. K is generally available to discuss his results and opinions. I'm sure he'd be happy to talk with your doctor.

I was discharged the next day and feel great, although my counts definitely took a dive. Even though Rituxan targets the CD20 proteins on B-cells, there is generally a broad spectrum affect on all blood counts (at least with the initial cycle) because the immune system goes into a hyper-drive response mode in the presence of the invading mouse protein component of the antibody. I assume the mechanism is some type of elevated phagocytosis but don't know for sure.

One week prior to the Rituxan treatment, I went in for my second bone marrow aspiration in as many weeks. With 4% hairies in the aspirate, I'm really hoping they can get the clone from this one so they can perform the patient specific hyper-sensitive MRD test in the future (1 cell in 1 million vice 1 cell in 10 thousand) when attacking the disease with Rituxan will have the best chance of eradicating it.

In other news, my liver enzyme tests have been consistently high for the past 3 months, so I'm starting to become more concerned. Tests for hepatitis antibodies have all been negative (thank goodness) so one possible remaining optionis that it's a temporary drug reaction caused by the Bactrim. I wrote to Dr. K asking if we could investigate other antibiotics, and he was very receptive and recommended a once-monthly inhaled drug in lieu of the Bactrim. We'll see if that returns the liver enzyme levels to normal.

Residual gluten in additives to the food I eat may be another factor contributing to the elevated liver enzyme levels. Many celiacs have very high liver enzyme levels prior to diagnosis as do people who are gluten intolerant. While I avoid gluten as much as possible, I'm not diligent in avoiding it all the time.

Interestingly enough, the product description for Bactrim also describes the fact that it sometimes has bone marrow suppressive effects, and I've seen anecdotal discussions that some patients have severe adverse reactions when they combine Bactrim and caffeine. Now I'm wondering if Bactrim was suppressing my marrow response after chemotherapy, and my recent experiments with caffeine to lower TNFa actually counter-acted a possible immune suppression effect Bactrim had on my marrow (I know, I know -- crazy mad-scientist and his theories). It'll be interesting to see if switching to the alternate antibiotic causes a dramatic acceleration in my future blood count responses.

Here're some plots of my most recent blood counts. Once again, my neutrophil count dropped when I reduced my coffee and chamomile intake in hopes of lowering my liver enzyme levels in preparation for the Rituxan therapy. Of course one day after Rituxan, everything took a nose dive, especially the lymphocytes. That's good, because the nasty hairies are part of the lymphocyte line of cells.

I've got seven cycles (1 per week) of Rituxan remaining. I'll keep you posted.

Miracles Happen!!!

2009-10-29T17:40:00.000-07:00

Good news! I had a bone marrow biopsy (BMB) and blood tests on Monday and Dr. K says my critical blood counts are all above the minimum thresholds for remission (even if the platelets and neutrophils are below the low-end normal standards). For remission, they use a platelet count of 100K vice 160K. For neutrophils, they use 1.5 vice 1.73. Still, we must get the results of my flow cytometry to determine the level of malignant cells still in the peripheral bloodstream before we can say for sure that it's a complete remission (CR).

The percent infiltration in my marrow is now 30% -- down from a peak of 80% one month after chemo. This is great news, but the level of infiltration is still very high, and I wouldn't be surprised if I relapsed within 20 months. I want to do something about it -- take Rituxan and eradicate it. Unfortunately, I believe the presence of disease in the marrow is used as a control for comparative analysis, not as a qualification for determination of Minimal Residual Disease (MRD) and treatment with Rituxan.

MRD testing is still in its infancy and uses less invasive flow cytometry of peripheral blood in lieu of bone marrow biopsy. Flow cytometry of bone marrow aspirate (BMA) can also be performed, but that is invasive. The goal is to make bone marrow biopsies after the first chemotherapy treatment for Hairy Cell obsolete by developing reliable hyper-sensitive MRD tests along with some other proprietary techniques. Hence, if my flow test does not show MRD, treatment with Rituxan will wait until it does, even though we know there is still significant disease in the marrow. This means the number hairies in the marrow may increase, although they very well may continue to decrease at this point.

The truth is I want my flow to show MRD so I can zap the hairies in the marrow ASAP. If the hairies in the marrow are continuing to die off, then the Rituxan will accelerate the process. If they have already nadired and are on the way back up, then I definitely want to hit them while they're still down.

Now for the bad news. They want more bone marrow aspirate before they treat me with the Rituxan so I've got to go back in for another bone marrow aspiration. That'll be my fourth in the past 7 months. I'm anxious to do it though, because I think there's a good chance it will help a lot with evaluating MRD in the future.

Here's a plot showing a very dramatic increase in the number of neutrophils since last week:

The NCI threshold for remission is 1.5. As you can see, my neutrophils are now at their highest level since I've been collecting CBC data. I'm very relieved, but I'm ready to keep going.

I'll keep you posted.

Update: I just received the peripheral and BMA flow results. The percentage of hairies in the peripheral bloodstream is down to .2%. The percentage in the marrow aspirate is 4%. Thus, MRD has been detected at 6 months post-chemo. I'll go in for another BMA procedure on Monday. The current plan is to see if the BMA hairies will clone before starting Rituxan. This will take a week, so we'll hold off treatment until November 9th.

Live Hard

2009-10-20T17:50:00.000-07:00

We've finally reached the 6 month post-chemo mark, and I'm feeling good. Since last month's post, I've had two CBCs and blood chemistry tests with some very interesting anecdotal evidence regarding caffeine and blood counts.

After my testing in August, I blogged about some research which indicated that caffeine can lower TNFa levels and hypothesized that since some research indicates that HCL apparently thrives on TNFa, maybe drinking coffee and consuming other TNFa lowering foods may improve or sustain my response.

The results from August to September were markedly improved. Upon seeing my liver function test results in September, I stopped taking the neurology drugs for my tinnitus and stopped drinking coffee and omega-3 supplements (fish oil has also been shown to lower TNFa). I was asked to come in two weeks later (September 29th) for a another blood sample so they could try to clone my hairies for PCR one last time before Rituxan treatments start, and they offered to do another CBC and chemistry as well (Nurse R went out of her way to arrange this for me). As shown in the plots below, my red counts, platelets and ANC all decreased in the two weeks between September 14th and September 29th, when I had ceased the coffee, chamomile tea and fish oil.

After getting the September 29th results, I decided to start taking the coffee, tea and fish oil supplements again before my next test, which was today. As you can see, there was improvement in all the counts from September 29th to October 23rd. Obviously this data is only anecdotal but nonetheless interesting in that it correlates with the presence of the anti-TNFa beverages and supplements.

Anyway, I'm now the proud owner of a Keurig single cup coffee brewer. I may even buy one for my office so I can avoid the battery acid that they try to pawn off as coffee. During the daytime, my co-workers know me as mild-mannered Mr. Coffee, not knowing my secret identity -- Java Man -- killer of hairy buggers everywhere (at least the ones in my bone marrow).

Tomorrow, I go in for my 6 month MRI, and my bone marrow biopsy (BMB) is scheduled for Monday, the 26th. Assuming it will take a week to get the pathology report, I expect to start Rituxan either Monday November 2nd, or the following Monday, November 9th. The first round will be administered over an 8 to 10 hour period, and I'll stay at the hospital overnight to make sure I don't have any adverse reactions. Many patients develop fever and vomit during the first round, but most respond with minimal side effects. After the first round, the time to administer subsequent rounds decreases to around 4 hours.

With respect to my daily activities, life is as normal as it's ever been. I haven't had a nose bleed in months, and even though my neutrophils are low, I still engage in pretty much all the activities I would have were I HCL-free. I try to bike 8 miles on Tuesday and Thursday and anywhere from 18 to 20 on Saturday. We've been to several county fairs and recently took Claire to a local Fall festival where we saw pigs and milking cows, rode slides and took a hay ride. I've added some pictures for everyone to enjoy.

Likewise, I'm pleased to announce that baby #2 is now on the way and doing very well -- just in time prior to starting the Rituxan. Once the Rituxan starts, natural conception must be avoided for at least 1 year. In the immortal words of Andy Dufresne: "Get busy living, or get busy dying." I choose to live hard.

Still Running Up That Hill

2009-09-28T15:15:00.000-07:00

My last blood test was two weeks ago and the results are mixed. On the positive side, all my red counts are now above the low end of normal and my neutrophils are higher than they were the day before I started treatment. This is good news which means the Cladribine must have had an effect on the hairy cells in my marrow. Unfortunately, all of my white counts (including the neutrophils) are still well below the low end of normal, which makes me a minor responder -- part of 5% of patients for whom Cladribine treatment does not result in a complete or partial remission.

The latest FACS results indicate that the level of hairies in my peripheral bloodstream is 0.25% (wrt mononuclear cells), so no change since late July. The binding capacity of my hairies for the anti-CD20 monoclonal antibody Rituximab (aka Rituxan) is still over 100k, which means the Rituxan should work well. Unless a miracle happens between now and my CBC and BMB in October, I will still have minimum residual disease (MRD) and undergo treatment with 8 cycles of Rituxan (once a week for 8 weeks), which Dr. K believes "may eradicate the disease."

I'm on cruise control now. Hopefully, the Cladribine has peeled away enough layers of the onion to let the Rituximab finish the job. The veins leading to my marrow that were once clogged with hairies (I compare it to hairy algae clogging the tubing in a fish tank) should be cleared out and ready to let the Rituximab into my marrow.

Here're my latest CBC plots:

I like the acceleration in the red counts. Maybe all that coffee and chamomile drinking helped after all...

I'm going back in tomorrow to have more blood drawn to see if they can clone my hairies for PCR before we start the Rituxan treatments. I'm not sure if this means none of the prior attempts worked or not. Maybe they just want to ensure that they have a "fresh" clone in case the chemo caused mutations or some sort of genetic natural selection in which the surviving hairies are somewhat altered from the general pre-chemo population of clones that were produced. The clones are used in the PCR process to detect 1 hairy cell from 1 million blood cells vice the current state of the art of 1 in 10,000.

If they get the cloning and PCR detection technique to work, it may lead to earlier detection and use of Rituxan as a standard therapy to attack the disease early on when tolerable doses of Rituxan alone can eradicate it. Of course there is always the argument that if the blood counts haven't been affected, there's no need to treate the disease, but if cure can be demonstrated, then this argument may need to be re-examined.

RF Radiation, Cancer and HCL Epidemiology

2009-09-04T07:07:00.000-07:00

Here's an interesting article from the Amateur Radio Relay League (ARRL) that discusses RF Radiation Safety and studies that address the association between high-level RF Radiation exposure and cancer:

http://www.wave-guide.org/library/arrl.html

Here's an excerpt from a study of the epidemiology of Hairy Cell Leukemia:

HCL risk was concentrated in white males; there were few black and Asian patients for analysis. Overall, the age-adjusted incidence rate of HCL for men (2.9/million population) was 4.8 times greater than that for women (0.6/million population). Using data from all cancer patients diagnosed during the study period, Jewish men had significantly greater risk of HCL than Protestant men.

For men, the OR was significantly elevated for professional and technical workers (OR = 2.1, P = 0.001); within this category of occupations, risk was significantly elevated for engineers (OR = 4.0, P = 0.0008). HCL patients were more than twice as likely to have multiple primary cancer diagnoses as other cancer patients. Since the majority of the other primary cancer diagnoses occurred prior to (>1 year) or concurrent with (1 year) the HCL diagnosis, this greater frequency of multiple primaries in HCL patients may be due to impaired immune function.

The One-Two Knockout

2009-08-28T21:07:00.000-07:00

Good news for patients who don't respond to Cladribine. I found a study citation that shows that even for minor/non-responders to 2-CDA, complete remission after treatment with Rituximab was achieved.

A study at the University of Pisa, Pisa Italy, studied a cohort of 10 patients who followed a treatment regimen very similar to the one I'm in at NIH. Patients were first treated with a course of 2-CDA (chemo) followed by Rituximab 6 months later. Here's the study citation:

Purine analogues have dramatically improved the outcome of patients affected by hairy cell leukemia (HCL), although complete eradication of disease was achieved in few cases. The purpose of this study was to evaluate the role of Rituximab in eradicating minimal residual disease (MRD) in HCL patients after a pre-treatment with 2-chloro-deoxy-adenosine (2-CdA). Ten patients received four cycles of Rituximab after administration of Cladribrine. Before starting anti-CD20 antibody, two patients were in complete remission, six in partial remission and two showed no significant response to Cladribrine. All cases resulted IgH-positive. Median time from the last 2-CdA infusion was 5.7 months. Eight of 10 patients [four in partial remission (PR), two in complete remission (CR) and two unresponsive after 2-CdA] were evaluable for response. Two months after the end of anti-CD20 therapy, all evaluated patients presented a complete haematological remission. Moreover, Rituximab increased percentage of molecular remission up to 100% 1 yr after the end of treatment. Interestingly, in all cases but one, including those persistently polymerase chain reaction (PCR)-positive, semi-quantitative molecular analyses showed MRD levels lower than those found before Rituximab administration. Toxicity was very mild. The present results not only confirm the therapeutic effect of Rituximab, but also show its relevance in eradicating MRD in HCL.

The really great news here is that of 8 patients, 2 were non-responders at 6 months post-chemo, yet all achieved complete remission after treatment with Rituximab biological therapy, and the toxicity was very mild.

There is still plenty to hope for, and I'm glad I found the NIH study.

Plan B

2009-08-26T18:15:00.000-07:00

A few months back I discussed how HCL thrives in the presence of a cytokine (cell signaling molecule) called tumor necrosis factor alpha (TNFa). Given my less than 3-sigma response to Cladribine, I thought it might be worth investigating foods and medicines that suppress the production of TNFa to help me bide my time.

I asked Dr. K (via e-mail) whether they monitor TNFa in the routine blood tests they perform. He said they used to but found the data to be not very meaningful. I assume this means there was too much variance in the data. I then asked him whether given the overall trend in my data, I'm considered a minor responder. He did not respond to that question.

I had read an article in Tallman and Poliak that discussed how TNFa reducing drugs given in parallel with 2-CdA improved response rates in HCL, so I did my own search regarding foods that lower TNFa and struck gold immediately.

As described in "Caffeine suppresses TNFa production via activation of the cyclic AMP/protein kinase A pathway", Horrigan et al, International Immunopharmacology, Vol. 4, No. 10-11 (October, 2004) pp. 1409-1417 -- coffee can suppress TNFa and thus may be helpful in suppressing the rate of cloning of HCL cells. The most caffeinated food (aside from sugar laden jolt and Red Bull) is restaurant prepared espresso. Here is the paper's abstract:

This study investigated the effect of in vitro exposure to caffeine, and its major metabolite paraxanthine, at concentrations relevant to typical caffeine consumption in humans, on lipopolysaccharide (LPS)-stimulated cytokine production in human whole blood. In addition, a role for the cyclic AMP/protein kinase A (PKA) pathway in the immunomodulatory effect of caffeine was investigated. Diluted whole blood (taken following >/=15 h abstinence from caffeine-containing food and beverages) was preincubated with caffeine or paraxanthine (10-100 microM) and stimulated with LPS (1 proportional, variant g/ml) for 24 h. The proinflammatory cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-12, and the antiinflammatory cytokine IL-10 were measured in cell-free supernatants. Whilst caffeine and paraxanthine had little or no effect on IL-10, IL-1beta, or IL-12 production, TNF-alpha production was suppressed in all individuals studied. The effect was statistically significant at 100 microM and consistent across seven experiments performed. Although not statistically significant, a similar effect was observed with paraxanthine. Caffeine (100 microM) also increased intracellular cyclic AMP concentrations in LPS-stimulated monocytes isolated from whole blood. Moreover, the effect of caffeine on TNF-alpha production was abolished by pretreatment with the protein kinase A inhibitor Rp-8-Br-cAMPS (10(-4) and 10(-5)M). To conclude, this study demonstrates that concentrations of caffeine that are relevant to human consumption consistently suppress production of the proinflammatory cytokine TNF-alpha in human blood and that this effect is mediated by the cyclic AMP/protein kinase A pathway.

I'm going to add one espresso a day to my morning routine in the hope that it will stop the strong cells from signaling further reproduction and infiltration of my marrow. With any luck, I might be able to tip the balance and hold off the stronger cells from reproducing while the chemo continues to take out the weaker ones. Then the Rituximab can come in and wipe out the cells that the chemo couldn't take out.

Foods containing Lutolein (a flavonoid) like celery, green pepper, and chamomile, also suppress TNFa. Other TNFa inhibitors include Nettle Leaf, and ECGC (found in Green Tea). Vitamin A also appears to help suppress TNFa production, which is also linked to the onset of diabetes ("Vitamin A may suppress type 1 diabetes", L. Crowley, Mar. 31, 2008).

I'll be adding all of these to my regular diet.

I wonder if previous studies of TNFa levels proved to be meaningless because diet can affect the levels. Without a controlled diet, studying TNFa levels may prove futile.

TNFa is also associated with demyelinating disorders such as multiple sclerosis and certain forms of tinnitus. Given the fact that Cladribine is effective in treating MS and HCL, I think a logical hypothesis is that Cladribine may somehow block TNFa signalling pathways, possibly by amplifying a protein kinase pathway. Perhaps in minor responders, there is a genetic difference which reduces this effect. A study of individuals who drank a V8-like beverage for 26 days showed they reduced their TNFa production by 34.4%.

Wish me luck!

Keep on Truckin'

2009-08-24T15:34:00.000-07:00

I underwent chemotherapy (Cladribine -- aka Leustatin) four months ago and although 99% of the malignant cells in my peripheral blood have died off, my bone marrow response has been very slow. Dr. K wants me to remain on a one-month blood work follow up. As you can see in the graph below, my platelet count is still hovering around 100. I think that the count may be deceptively low because the platelets may be aggregating and fooling the FACS into counting what are multiple aggregate platelets as a single platelet. I'm going to ask Dr. K if he can order a peripheral smear slide examination (direct microscope examination by a pathologist) to see if this might be the case.

The good news is that my WBC, RBC, neutrophil and other counts continue to increase, although slowly. Some other counts, like Basophils, that were previously imperceivable, have now started registering.

Full disclosure -- I took 100 mg of grape seed extract (GSE) per day for a week back in June -- after my platelets had gone to 131, but before the next test showed them crashing back down to 100. Dr. K didn't have a problem with it (probably because he doesn't think it'll do anything), but given GSEs apoptotic effects on Jurkat leukemia cells, I thought it might also help destroy HCL cells too. The studies conducted by City of Hope indicated that GSE wouldn't harm healthy cells; however, I'm concerned that the GSE might have somehow knocked down my bone marrow's progenitor cell production. Still, there hasn't been enough data collected on GSE's effects in humans to know for sure.

I found an article addressing the efficacy of injecting Cladribine intravenously -- "Treatment of hairy cell leukemia with cladribine (2-Cda) by subcutaneous bolus injection: a phase II study," by Rohr et al, Annals of Oncology, 2002. I believe it is the basis for Dr. K's decision to use this method of administration in his clinical trial. The median time to failure for this approach is approximately 38 months. That sounds bad, but I think what it really means is that once a complete remission is achieved, it usually takes 38 months before any malignant cells are detected again. It may take much longer before the marrow and blood counts are affected, requiring a second round of chemotherapy.

Using this approach resulted in an overall remission rate of 97% (76% complete, 21% partial). Complete response requires the dissapearance of all evidence of disease, a return to normal peripheral blood counts, and the absence of hairy cells in the blood stream and the bone marrow. Time to failure is defined as the time between treatment start and progression, relapse, second tumor, or death, whichever occurs first. A partial response also requires a return of all blood counts to normal, but the reduction of cells in the marrow is somewhere between 50 and 99 percent.

PRs and CRs usually occur within 10 weeks after chemotherapy, so I'm bummed because it's been 16 weeks and my blood counts are still below normal and malignant cells, however slight, are still being detected in my bloodstream. That makes me part of the 5% considered minor/no response, so I'm glad I'm in the trial. Hopefully, what the Cladribine doesn't kill, the Rituxan I'm getting in October (once a week for 8 weeks) will.

(More at the bottom of this blog post...)

I've lost a total of 16 pounds over the last two months -- mostly excess fat. I'm down to 188 pounds and holding steady now. My endurance is great, but I have been feeling dizzy lately. I'm anxious for my next bone marrow biopsy in October and to get started on the Rituxan.

I also have a theory on what may have caused my leukemia. Several fellow HCLers have written to me noting that they are also RF engineers or hobbyists, wondering if there may be a common association between our line of work and the disease. A common factor in all of us is that we experienced high-power RF burns over 10 years ago. Likewise, electrical linemen also seem to have a slightly higher incidence of leukemia. Back in 1998, I received a 20 to 40 Watt RF burn at 137.5 MHz when a fellow engineer indicated he had turned off a transmitter but had not. When I disconnected the transmitter's output cable to reconfigure the system for another test, I received a severe RF burn on my hands that took several weeks to heal. In some people, RF burns may cause cellular mutations and induce HCL, but until some meaningful data is collected to prove this, I won't know for sure.

Regardless, bad things happen every day. You just have to accept it and keep on trucking.

KOT!

The Cost of Hairy Cell Leukemia

2009-08-18T19:04:00.000-07:00

I reviewed all my insurance statements since my first doctor's appointment that led to my diagnosis and treatment for HCL. The total diagnostic cost billed by the doctors was $19250. Add the "virtual" cost of the NIH provided chemo at $5,000, the 1-month BMB at $1500 and the follow-on CBCs at $2000 along with $2500 for "progeny insurance" and the total is around $30260.

The insurance negotiated diagnostic costs came in at $4120 -- a $15,130 savings vice the doctor charges.

Given that I haven't submitted my "progeny insurance" claims yet, my total out-of-pocket (OOP) expense thus far is $2695. A savings of $42565, which may increase when I submit the other claims. My total OOP expense could be as low as $195. Not bad. Say what you want about insurance companies, but I'm grateful for mine. Without their negotiations and coverage, HCL would have left me bankrupt.

What I don't understand is why the initial doctors costs are so high compared to the negotiated costs. The variance between insured negotiated costs and uninsured non-negotiated costs is beyond reason. That the people who can afford it the least are left paying the most when their health turns for the worse is immoral given the large arbitrary cost fluctuations that exist between the insured and non-insured.

Following up on my last blog, my ALT and AST levels after going off Clonazepam were very good -- 24 and 28, respectively, so I've switched from Clonazepam to Gabapentin, which doesn't metabolize. I go in for my 4-month CBC tomorrow. I'll post the results once I get them.

3 Months Post-Chemo and Counting

2009-07-31T19:02:00.000-07:00

It's hard to believe 3 months have passed since I underwent chemotherapy. I had my last blood tests on July 22nd, and the results were mixed. The good news is that about 99% of the malignant cells in my peripheral blood have been knocked down, and blood count-wise things are not getting worse (although I do have some questions about my T-cell ratios).

Each month the rate of reduction in the malignant cells has decreased by half. The first month 98% of the remaining hairy cells were destroyed, the second month 50% of the remaining hairy cells were destroyed, and the third month 25% of the remaining hairy cells were destroyed. I'm gonna go out on a limb and guess that this month 12.5% of the remaining hairy cells (of which there are very few) will be destroyed.

The bad news is that my blood counts aren't really that much better than last month. My white cell count is still about one-third of normal. Still, I've got 3 more months to improve, so I keep reminding myself I'm only halfway there. My liver function tests (AST and ALT levels) came back very high. I'm assuming this is because of the Clonazepam I've been taking to help me sleep, so I stopped taking it for the past week. I'll stay off it until I have my primary care doc do a liver function test next week.

I've lost about 16 pounds since chemotherapy. I simply can't eat enough while I'm at work to keep up with what my body needs. On the bright side, I'm back to working full days on some very interesting NASA science and technology satellites -- NuSTAR (to research the super-massive black hole at the center of our galaxy) and GLORY (to research Earth's aerosols, clouds and irradiance).

I'm really not too concerned about the low neutrophil count anymore. It seems to be slowly increasing, and from all accounts, I'm more susceptible to infections from germs already in my body than external pathogens. Christi, Claire and I went with our friends to the water park last week and had a great time splashing, sliding and playing in the water. I made sure to slather myself in sunblock spray to maintain my lovely pasty-white complexion. It's my sworn duty as leader of the Pasty Boyz.

The following charts show my blood count progress up to the last blood test:

Typically at 3 months, the WBC count is close enough to normal to warrant only testing the peripheral blood 3 months from now, but in my case, I need to go back in 3 more weeks (1 month since the last one).

On a good note, I can workout on my elliptical and exercise bike much more easily than I used to. About two weeks ago, I rode 20 miles on my exercise bike on interval training at about 75% of the bike's full resistance. I'm very anxious the get back to the Grand Canyon and see what I can do once my RBC recovers to a normal level.

Last June, I hiked an hour into the Canyon and it took me about two hours to hike back out. I had to stop and rest about every 200 feet to catch my breath and keep going up. At that point, I was already probably below normal on platelets, and I'm sure my red count was suffering too. Thank God my friends were there to share their water with me and keep me going.

It was exhilarating to make it out on my own two feet -- knowing that my friends were there to pull me through; but I was left wondering "How come it was so much harder for me than everyone else?" Certainly, sitting for 12 hours a day at work didn't help, but I kept wondering if something else was wrong. I wasn't really dehydrated, my legs just got tired really easily. Two days later, 4 people died when a medivac rescuing a hiker from the Canyon was trying to land and collided with another copter taking off from the Flagstaff Hospital. Without the right friends, that could have been me.

HCL and Secondary Cancers

2009-07-10T16:58:00.001-07:00

A lot of the HCL blogs and discussion boards that I follow have patients who want to know more about secondary cancers, so I thought I'd do some more research into the subject.

An intensive study was conducted by NIH which examined the risk of secondary cancers in 3104 2 month + survivors of HCL. It found that the cumulative probability of a secondary cancer in 25 year survivors was 32%, but not everyone in the study lived that long. Most patients usually die of other natural causes first, but the finding is a major bummer for the younger than average patients like myself. Statistically, the mean follow up time with patients in the study was 6.5 years. Some died, some moved, some stopped participating out of apathy.
Standard incidence ratio (SIR) is a term used to compare the rate of a cancer among a particular group to the general healthy population; hence, for healthy average Joes, the SIR of a particular type of cancer is one. For HCL'ers, the SIR for Hodgkin lymphoma is 6.61 (6.6 times more likely to get it than a normal, healthy individual). The SIR for non-Hodgkin lymphoma is 5.03. Thyroid is 3.56. Lucky for me, the SIR for lung cancer is less than the normal population, coming in at only 0.63, but that's probably just due to the fact that people stop smoking when they find out they have leukemia -- a macroscopic trend which doesn't really transcend to individual risk reduction. Overall, the SIR for all secondary cancers over the HCL population is 1.24 -- or 24% greater than average.
In fact, HCL isn't the first cancer I've been treated for. I was treated for a basal cell carcinoma (BCC) in late July, 2007, so it's likely I've already experienced a secondary cancer from HCL even though it was treated prior to the official HCL diagnosis. BCC is a type of skin cancer which doesn't metastasize but can become disfiguring if left untreated. One of the nurses at NCI told me they tend to see more than the average number of skin cancers in patients with HCL. Be forewarned, I'm going to show you some pictures of my surgery below, so if you're squeemish, don't read on.
My BCC started as a persistent pimple on my left nasal ala -- mainly in the crease between my nostril and cheek. Over the course of several months, it gradually turned into a surface rash that sometimes bled when I showered -- cycling between healing and bleeding. At the time, my platelets were already down to the low end of normal, so this may have exacerbated the bleeding. Soon, I started feeling throbbing in the region and feared that veins to a tumor might be forming so I went in to get it checked out. With one look, my dermatologist knew she had to take a biopsy and sure enough the pathologist determined it was cancer.

As promised, here are the pre-close and post-close pictures from the Mohs surgery. Mohs surgeons are trained pathologists. This is required because the surgery is conducted in multiple phases to minimize cosmetic impact while ensuring that all the roots of the cancer are cut out. The surgeon uses a special dye to examine each sample of excised skin under a microscope and ensure that enough healthy margin exists at the edge of the cancer.

My surgery took 4 phases because it was rooted much deeper than anticipated. I was lucky that it was in the crease of my nose. The doctor did a great job, and most people can't even tell that I ever had surgery. It took extra long for him to cauterize my flesh and stop the bleeding, and he noted that to me when he did the surgery. That led to my Dr.'s appt. in October of 2007 which first noted that my platelets were at the low end of normal (140). Come to think of it, I think that's one of the reasons I demanded a CBC (or "the works" as I called it) at the time. Here's a link to a short video on Mohs surgery.

Anyway, I don't want to scare any of you HCL'ers out there, but you do need to be aware that you should take extra precautions, avoid the sun moreso than others, and live as healthy a lifestyle as possible after treatment.

My next blood test is in two weeks. I follow a lot of the discussion groups and many fellow HCL'ers who were treated at the same time as me are already in remission. I'm jealous but very hopeful that my blood tests will show significant improvement next time.

Numberz

2009-06-27T08:26:00.000-07:00

I thought I'd share a few plots I've generated of my various blood counts. First, the white blood cell (WBC) count data. As you can see, the WBC was below the low end of normal prior to chemotherapy and is currently holding at ~1000 cells/uL. I've got a long way to go to get back to normal (the red line).

Next, the RBC counts. My red cells are also below the low end of normal but seem to be holding out. Based on the current trend in the curve, it looks like they may start to come back up soon.

Now for the some good news. My platelets are back on the rise, and they're the harbingers of recovery so this is a good sign.

But of course, the neutrophils have to put a damper on everything. Still, the rate at which they're declining is decelerating, so we should see a U-turn soon.

Lastly, the lymphocyte count is 30% of the low end of normal. Most of what's left (95%) are T-cells (that's what the report said). NK cells make up 4.5% and B-cells make up only 0.5% of the remaining lymphocytes. That's fine with me. It's a B-cell that mutated into a hairy cell and got me in this mess, so I'm not such a big fan of them anyway.

The Light at the End of the Tunnel

2009-06-23T17:50:00.000-07:00

Even though my neutrophils are pretty low (660), I decided to go on a bike ride this past weekend up to the Paw Paw Tunnel in West Virginia. I planned the trip about a week ago, after talking to a Park Ranger at the Lock 8 gatehouse on the C&O canal. Initially, I only planned on doing 6 miles because I didn't want to push too hard, but once I got going I didn't want to stop. I ended up riding 15 miles and loved every minute of it. There's a beautiful view of the Potomac River, and the entire path is shaded by towering trees.

The solitude and grinding of the greystone beneath the bike tires takes your mind to another time. With the faint smell of decaying leaves and campfires in the breeze, thoughts about the legend of Sleepy Hollow entered my mind. I was racing away from some unseen adversary. I found the tunnel website about a day before the trip and that's when the metaphoric irony of where I was going hit me. The description mentioned the "light at the other end", and I knew I had to go.

The drive up was beautiful. The sky cleared about half-an-hour before I got there, then I toured the tunnel and boardwalk for about 45 minutes on foot before riding. The weather held out, although I had to race some storm clouds, and a train on the other side of the river, on the way back. The train won, but I beat the clouds. If you decide to go, make sure you take a flashlight or preferably a headlamp if you're riding.

Enough self-indulgence for one day. Now for my latest medical status. I received the results of last week's FACS (2 months post-chemo). The number of hairy cells in my blood is still going down, but slowly. The green 'FACS' curve below shows the numeric density of my hairy cells (cells per micro-liter) and is the most important factor as far as I'm concerned. The red curve shows the percent of mononuclear blood cells which are hairy cells, which is essentially meaningless unless you know the WBC count. The x-axis values are days since start of chemo.

My HCL FACS Data

The 'FACS' curve shows that the numeric density of hairy cells has decreased 65% over the past month (days 28 to 56) and 98.1% since the peak value 2 days before chemo started. I was hoping the number of cells would be even less and only detectable via PCR, but as long as the numbers keep going down, I'm happy.

Side Note: A two-year Phase III clinical trial using Cladribine (the chemo drug for HCL) to treat Multiple Sclerosis (MS) is showing lots of promise for effectively controlling the relapsing-remitting form of the disease. The approach uses a pill form of the drug. I believe the underlying theory is that MS (and most auto-immune diseases) are caused by overactive B-cell lymphocytes, which Cladribine kills very well. A fairly innocuous chemotherapy (with respect to physical effects like vomiting and hair loss) in pill form can effectively reduce the severity and relapse rate of the disease. This will provide relief to many MS patients since current treatments require injections with drugs that are difficult to tolerate.

I go in this Thursday for another CBC. As always, I'll keep you posted.

Counting Backwards

2009-06-18T13:34:00.000-07:00

Just got my latest CBC results. Not very encouraging...

Neutrophils fell from 880 down to 660 (good is 2000)
Lymphocytes fell from 450 to 380 (good is 1500)
RBC fell from 3.85 to 3.73 (good is 5)
WBC fell from 1.38 to 1.1 (good is 6.0)

Platelets went up from 87 to 97. (good is 160)

Count wise, everything else stayed about the same.

My cholesterol was better:
HDL is up to 30 from a low of 18 (that's better)
LDL is down to 31 (anything less than 100 is good)
Total cholesterol is 88 (less than 200 is good, but very low is a disease marker)
and triglycerides are at 133 (normal)

The original protocol plan was to have another CBC 4 weeks from now, but given my slow and backward progress, we're having another one done next week.

Pushing rocks is exhausting, and I'm not getting that golden tan that they promised either.

The HCL Rap...

2009-06-17T20:14:00.001-07:00

If only I could get Andy Samberg to produce this...

(Reads like an SNL Short Rap)

Hairy Cell Leukemia
ain't got nothin on me (echo Denzel audio clip from training day)

Killin' you with Cladribine (picture of chemo treatment and 2-CdA)
just wait and see

You're crowdin out my marrow
but that's okay,
'cuz In the end you're gonna die
I got Dr. K (show picture of Dr. K)

Givin' you a left hook (Shot of Rocky hitting Drago)
with Rituximab
I'm takin' you out...
You ain't so bad! (clip of Rocky yellin' 'You ain't so bad' at Clubber Lang)

They're taking blood
week after week
and vial after vial

I can't believe I got you,
but I'm not in denial

Don't try to run
'cuz I'm gonna cream ya

for causin' marker diseases
like hypocholesterolemia

Bone Marrow Biopsy? (show a clip of a biopsy)
I say "Bring it On" (echo clip of Bush saying 'Bring it on')

I'll take you on and kill you
it won't be long

Monitorin what's left
with flow cytometry (show a machine in action and Bruce Willis sayin 'Just the Fax, Maam')

When I'm killin you
I know it
'cuz it gives me green pee (picture? nah, better not)

Don't try to hide,
I'll find you
with PCR

when you're one in a million,
I'll still know where you are

Think that you're the chronic?
Well, don't even try it

Gonna eliminate you
like I did Gluten from my diet

Got a beautiful wife (picture of Christi)
and a baby-doll girl (picture of Claire)

Gotta live til I'm 70 (morph me from now til then)
so I can show her the world

I'm pushing the rock
and It's gonna move

H-(pause)-C-(pause)-L?
Well I got somethin to prove

10 years ain't enough
25? I need more!

That's why I'm in this trial
to find a cure, cure, cure, cure ...

Pushing the Rock

2009-06-11T20:07:00.000-07:00

Had my neck ultrasound and CBC today. Zed (the mass in the neck) is dead. The radiologist believes Zed was just an artifact of blood flowing through the jugular bulb at the valve in the vein. That's good.

My blood counts seem to be settling back to their pre-chemo levels. The platelets fell all the way back to 87 -- down from 136 2 weeks ago. That's bad. Fortunately, my neutrophils have climbed higher, but only up to 880 (up from 795). They seem to be leveling out to where they would be had I not had the chemo. The reds have also inched back up, but only slightly. Apparently, I'm responding much more slowly than most, if at all. While it's true that the hairy cells in my peripheral blood have gotten knocked down quite a bit, it doesn't look like my marrow has responded very well, and that's the part that matters.

Next week will be another CBC with flow cytometry. I'm feeling down but not out. In the meantime, I'll keep pushing the rock.

What a pain in the neck this is...

2009-06-09T17:41:00.000-07:00

Okay, it's not really a pain in the neck, it's a small mass on the left hand side of my neck about 1.4 centimeters in diameter. Dr. K found it after running CT scans of my neck and chest on 5/22 after I complained of the fevers and aches and their impact on my work. At the time, he was concerned I might have been developing pneumonia.

Hopefully, the mass is just aggregate HCL that will eventually die away as the chemo does its job (per Dr. K). I'm going to have an ultrasound done on Thursday (6/11) when I go in for my next CBC to track its size and see if it's 1) larger 2) smaller 3) unchanged.

One would assume that if it's smaller, then the HCL theory holds water; otherwise, proceed with Plan B (currently TBD).

In the immortal words of John Proctor, "More weight!" Lucky for him, he was fictional.

Just the FACS m'aam

2009-05-28T17:42:00.000-07:00

FACS: Fluorescence-Activated Cell Sorting

FACS is a precise technique which is able to individually differentiate cells taken from the peripheral blood stream. It examines each cell individually, then categorizes it. It works by aiming a beam of light at a droplet containing a single cell and then examines the reflected light pattern. The light pattern is unique to the various types of cells in the bloodstream; thus, each cell can be categorized. It's able to examine millions of cells over the course of several hours.

One of the advantages of participating in the NIH HCL clinical trial is that in addition to the weekly CBCs, my blood is periodically examined using this form of flow cytometry. It's able to identify the individual hairy cells and determine the hairy cell numeric density in my peripheral bloodstream (the blood in my veins, not the marrow).

Because of the number of patients and hours required, it takes awhile to prepare, run and get the results of this test. I just got the latest results from blood drawn on 5/20, and the results are very promising. The table below gives a summary of the hairy cell numeric density before treatment, on Day 4, and 3 weeks post-treament.

Date FACS HCL count
4/20/2009 78.5
4/27/2009 40.1
5/20/2009 4.1

This means the density of hairy cells in my bloodstream is almost 1/20th what it was prior to treatment. The cladribine has definitely had an impact on the blood in my veins. Let's hope it's only a matter of time before the marrow shows similar progress!

The hope is that in 3 weeks, the number of cells will be immeasurable using FACS and a cloning technique known as polymerase chain reaction (PCR) will be required to find the hairy cells. The PCR technique being used at NIH is very sensitive -- able to find 1 hairy cell from 1 million regular blood cells. Prior to accepting me into the trial, Dr. K had to verify that they could develop PCR primers specific to my cells and then clone my cells in a reasonable amount of time. This highly sensitive technique will allow them to identify the faintest amount of minimal residual disease (MRD) and treat it with Rituxan at the 6 month post-chemo epoch or any time MRD is detected thereafter, according to the protocol.

Side Note: Interesting news for those of you dealing with solid tumors. I read another article on Grape Seed Extract today. This one discussed how it has anti-angiogenic properties. It arrests signals that solid tumors use to grow veins to nourish themselves, thus causing the tumors to starve to death. Here's the link.

The Good, The Bad, and The Ugly

2009-05-26T18:18:00.000-07:00

The Bad: I lost a total of 8 pounds from Friday the 15th through Saturday the 23rd. It all started with bone pain and muscle aches around 5 o'clock that Friday. At work, I had to hunch over when I walked and take small steps. I went straight to bed when I got home and took my temperature, which was 98. Not too bad for me since my normal temp is 97. By 8 o'clock I felt like I was burning up so I took it again and it was 100.1. Nothing too alarming, but given how abnormal it was, I called Dr. K to find out if I should be concerned. He didn't think so and told me to call him in the morning if it went above 101. It didn't, but for the next few days, it kept oscillating between 99 and 100.5. I lost my appetite and didn't eat much between Friday and Wednesday. I felt better on Thursday and Friday, but still wasn't feeling as good as before. By the time I got around to weighing myself on Saturday the 23rd, I had dropped 8 pounds.

The Ugly: On Wednesday the 20th, I went in for my 1 month post-chemo bloodwork and bone marrow biopsy. The CBC results showed the overall WBC count hadn't budged in 10 days, which was very dissapointing; however, my neutrophils did edge up a little bit -- from 450 to 680. My platelets remained at an intransigent 105 (same as 10 days before). Then came the BMB. They took it from my left hip this time. It was a dry tap. No marrow (the jelly-like plasma inside my bones) could be aspirated. This scared the Hell out of me. I thought for sure that plenty of hairy cells would have been killed off by now and the marrow factory would have been back in some degree of production. After all, my CBCs since chemo had shown some progress even if the past 10 days were marginal, but then again, maybe everything in my blood was just settling back to the pre-chemo levels. After augering out the core, they tried to aspirate marrow four times to no avail -- it came up dry each time. On the 4th try I could really feel it burn. "You're almost there," I said, but they gave up because they didn't have a longer needle to go any deeper.

The uglier: Today I got the biopsy report for the core sample. It read "80% infiltration." Eighty percent? That's more than when I was diagnosed back in March! What the Hell is going on? "Don't worry about it" they tell me. "Sometimes it takes months to respond." Then why do you take the BMB at 1 month? Can you take another one next month? "No." Why not? "We'll take another one in 5 months." I'm confused and to top it all off, my total cholesterol is at an unbelievably low 71 mg/dL. Most people are happy if it's below 200, but I don't think my level of 71 is something to be happy about because my HDL (good cholesterol) is only 18. This is a dramatic drop from 28 just a month ago. A healthy level is 40 or above with a low risk target of 60 or higher. Dr. K admitted he doesn't know much about the cholesterol/HCL relationship and doesn't seem interested in pursuing the subject. He attributes my low level to inactivity, but didn't bother to ask me what my activity level has been. I haven't changed my activity level at all, other than getting sick for 4 days. With the exception of the sick days, I've either done 2 mile walks, or worked out for 30 minutes on the elliptical and exercise bike every other day. My request for a referral for a specialist who can help me went unanswered. I suppose that sometimes research scientists are so focused on one aspect of a disease that they can't be distracted by patients various requests, or they simply forget.

The good: My brain MRI was negative. There was a small signal in my front right lobe, but my neurologist assured me that this is very common and nothing to be concerned about. My tinnitus appears to be idiopathic, so he prescribed a sedative that may help to address the symptoms. Overall, it's helped me sleep, although I did awaken to a sharp single tone the other night. I had another CBC today. The white count edged up to 1.42 from 1.28 over the past 6 days. The platelets are now at 136, which is a number my body probably hasn't seen since November 2007. The absolute neutrophil count (ANC) is back up to 800. Something must be working. Hopefully, whatever it is, it's working on the marrow and not just the peripheral blood systems, but the BMB report is inconclusive at this point. For now it's just a game of "hurry up and wait."

My next CBC is in two weeks.

Back to Work...

2009-05-16T07:19:00.000-07:00

Sorry it's been awhile. I started back at work this week and haven't felt like updating the blog.

I got my CBC results back on Monday. The WBC count is up from .97 to 1.29 of which my neutrophils more than doubled from 190 to 450. My platelets are up to 105. That's all good.

I've been suffering from tinnitus (ringing/buzzing in my ear) in my right ear since mid-March, and it seems to have gotten louder and more annoying over the past month. Sometimes I awaken in the middle of the night to loud ringing in my ear. As I sit here typing, an annoying white noise is resonating in my head.

To make sure the tinnitus isn't due to anything more serious, I went to see a neurologist in early May and had an MRI done this past Thursday (5/14). I'll get the results next Thursday. The tinnitus is probably due to getting older and nerve damage I've incurred from prior ear infections (no thanks to the HCL), but I just want to be sure nothing else is going on.

Ever since the MRI, I've felt weak and achey in my bones. I still do now. At work, I had to shorten my gait to reduce the pain when I walk, and I had a mild fever all night last night and felt miserable -- kind of like a fever combined with growing pains. I usually read 96.5 to 97.1 on the thermometer, but popped up to 100.1 and stayed there until this morning. I completely lost my appetite. Up until Thursday, I was eating around the clock just to maintain my weight. I definitely think I'm burning a lot of calories keeping the marrow going. Dr. K. thinks my marrow may be working in overdrive right now and causing the bone pain. He didn't seem to think the fever was due to an infection but told me to watch it and call him if it goes over 101.

Aside from the leukemia, I've also noticed that in the 3 months since I've gone gluten/wheat and peanut free in my diet, I haven't had a single canker sore (mouth ulcer). Canker sores used to be a common occurence. I used to get one every 2 to 3 weeks prior to going gluten and peanut free. They were incredibly painful and made brushing my teeth a nightmare as the bristles would scrape over the ulcer and agitate it even more so it wouldn't heal. Here's an article which discusses the causes of canker sores, which includes peanuts and gluten sensitivity.

I go back to [the clinic] this Wednesday for a CBC, abdominal ultrasound, EKG, bone marrow biopsy and clinic appointment. It'll last the better part of the day.

Killing Tribbles

2009-05-04T14:31:00.000-07:00

I had my blood tested this morning and got the results this afternoon...

Q: Is there anything lower than absolute zero?
A: Yes, my white blood cell count!

I've been feeling great ever since I had my last chemo 1 week ago, but my white blood cell count has definitely taken a beating. In particular, my absolute neutrophil count has tumbled from 1.05 down to .19. The normal range is 1.78 to 5.38. Dr. K says that this is to be expected with the Cladribine, so nothing too unusual, and it looks like the type of pattern that suggests a path to remission. In fact, he doesn't see any reason why I shouldn't return to work since most infections in HCL'ers are from internal pathogens. He recommended avoiding crowds and direct contact as much as possible. I'll verify this with my regular hemonc just to be on the safe side. I suppose I'll have to put off the County Fair 4H pig wrestling fund raiser until next year...

Overall, the composite WBC count nose dived from 2.34 down to .97 over the past week. The normal range is 4.23 to 9.07. Dr. K. indicated that days 12 through 17 are typically the low points for all counts, so these should start to level off and come back up starting next week. I've read so many horror stories from fellow HCL'ers posts that I'm not sure if I should go back to work or wait out the next week, but Dr. K doesn't seem to think work will be a problem. If I get a fever (which I haven't yet), I should just give him a call, and they'll bring me in and treat me.

The good news is that my red cells and platelets didn't budge. I guess that's why I feel so good. Dr. K has a feeling that I'll recover faster than most.

Anway, nothing clear-cut at this point, but nothing abnormal either. I've got my 3M 1860S surgical masks ready regardless... (got 'em on Amazon for 1/10th the regular price before they became the official mask of the 2009 Swine Flu Epidemic).

Chemo -- Day 5 and I feel fine

2009-04-27T15:32:00.000-07:00

The Cladribine (chemo) treatments are done. Overall, I felt more sensitivity when hooked up to the saline solution than the actual chemo, and I'm not kidding. I actually feel full of energy right now, but that's not to say that my counts haven't been affected -- they have.

Lots of blood was drawn before today's treatment. Dr. K wants to see if any of my antibody levels have been affected by the Cladribine. Apparently, my blood is very interesting. I should have patented my gene sequences before I signed up (ha ha). As mentioned in Paul Edward's HCL blog, this disease was involved in the first case of human gene patent rights. Recalling the major details, I believe doctors at The University of California kept asking an HCL patient to return to give more blood under somewhat false pretenses but all the while, they sequenced his genes, patented them and then made money off it. The patient sued to have the rights to his own gene sequence and future profits and lost. Anyway, I only care about staying alive, so the CBC results are what matters.

Here's a before and after look at my blood counts based on levels taken right before chemo started and after Day 4:

Cell type, Pre-Chemo Value, Day 4 Value, Normal Range, Percent Change
WBC 3.34 2.38 [ 4.23 to 9.07] -28.7
RBC 4.21 3.93 [ 4.63 to 6.08] -6
HGB 13.6 12.6 [ 13.7 to 17.5] -7.4
HCT 39.5 36.0 [ 40.1 to 51 ] -8.9
MCV 93.8 91.6 [ 79.0 to 92.2] -2.3
RDW 14.2 13.9 [ 11.6 to 14.4] -2.1
Platelet Count 87 89 [161 to 347] +2.3
Neutrophils 31.4 48.3 [ 34.0 to 67.9 ] +54

Lymphocytes 63.2 47.1 [ 21.8 to 53.1] -25.5
Monocytes 4.5 2.5 [ 5.3 to 12.2] -44.4
ANC 1.05 1.15 [ 1.78 to 5.38] +10
ALC 2.11 1.12 [ 1.32 to 3.57] -47
AMC .15 .06 [ .30 to .82 ] -60

The important point here is that my Neutrophil count and platelets have remained rock steady, so it doesn't look like I'm at risk for extreme neutropenia or hemorrhaging. Let's hope this holds out as I recover. Also, my hemoglobin and RBC, although low, are in pretty good shape and should return to normal soon.

I'll have weekly CBCs for the next few months and another BMB on May 2oth. Let's pray it shows significant remission. Yet another BMB will be taken on October 23rd. If hairy cells are again detected, I'll receive 8 weeks of Rituximab treatments (1 per week), but this won't occur sooner than October 23rd because the effects of Cladribine continue to be significant for about 6 months.

Chemo Day 4 -- See Day 3

2009-04-27T06:15:00.000-07:00

Chemo day 4 -- please see day 3, then add a nap between 5 and 7 pm.

I go in today at 12 for my last chemo and to get blood drawn. Woohoo!

Chemo -- 3 down, 2 to go

2009-04-25T15:27:00.000-07:00

Day 3 came and went without a hitch. I drank plenty of water in the morning and got to the day hospital at 12:00. The nurse unwrapped the ace bandage and tested the IV for blood flow with a syringe of saline. At first it didn't flow, but when she pressed on the vein slightly, everything worked fine. She hooked up the Cladribine and I was off and running by quarter 'til one.

Everything went great and I feel pretty good, so I must still have plenty of red blood cells even if my whites are down.

Hopefully the chemo is doing its job.

Chemo Day 2 -- Ouch

2009-04-24T17:28:00.000-07:00

Note to self: drink lots of water before IV placement.

I lost track of time this morning and forgot to drink plenty of fluids before chemo today. That's bad. If you're dehydrated when getting an IV placed, the valves in your veins are much more sensitive to fluid pulling in the wrong direction and they'll seal tight like the vaults at Fort Knox. And when the valves seal up, the catheter in the IV usually won't go in. If it does go in, the fluid in the IV won't flow. I found this out the hard way 4 times today. 1 1/2 hours and 5 cups of water later, we finally had success on the 5th try. If you already guessed that I didn't have the IV taken out after today's treatment, you're right. It's bundled nicely in neon-blue ace-wrap to prevent it from ripping out. Let's hope I don't toss and turn too much tonight. Tomorrow, I'll wrap it up nice and tight in Saran wrap a couple times and then shower. Ya gotta do what ya gotta do.

Other than that, everything went well today. The food at the hospital was slightly better, and I read a good joke, too:
Q: Do you know what the difference between an oral and rectal thermometer is?
A: The taste.

Okay, sorry to gross you out, but man that made me laugh.

Christi and I picked up Claire from daycare today, and it was great to see her again. Grandma and Papa took good care of her Wednesday and Thursday night while Christi and I adapted to the on-the-fly schedule changes needed to enter the trial. Thanks Grandma and Papa! The first thing Claire wanted to do when she got home was sweep the floor with the broom and sing "Itsy Bitsy Spider." After dinner, we went for a nice walk.

My neutrophils fell to 1.0 on Wednesday, so they're likely even lower now that I've had 2 rounds of chemo. I should get a complete report on Monday, the last day of chemo. The real danger zone with neutrophils is 0.5 or lower. At that point, no eating out, cook food thoroughly, no raw vegetables, and no fish. Hopefully, I won't drop below .7. Regardless, I'm avoiding crowds and contact with others for the time being (especially now that the Mexican swine flu has me freaked out). My doctor has prescribed an antibiotic, Bactrim, that I'm to take for the next 3 to 6 months on Mondays, Wednesdays and Fridays at 9 am. It's intended to prevent certain bronchial infections that would otherwise be devestating if not stopped early on.

That's all for today. I still haven't felt many side effects from the chemo. I expect that after tomorrow, some serious lethargy will start to kick in, but we'll hope not.

Til tomorrow

Chemo Day 1

2009-04-23T19:16:00.000-07:00

This morning I called LabCorp to see if I could track down the H&E stain slide that they used for my original bone marrow biopsy (BMB) report. They could not find any record of me having a BMB in their database. I called my hemonc's office to see if they could provide me with their point-of-contact at LabCorp that they used to coordinate the original slide shipment. They couldn't find it. My hemonc's lab technician called LabCorp to see if he could make any progress, but LabCorp kept switching him back and forth and never connected him to the right person. Personal conclusion: LabCorp is a 3-ring circus and has a horrible electronic records capability. United Healthcare (my insurance) needs to switch to Quest Diagnostics. I'm going to write them a letter to that effect.

My hemonc did provide me with a copy of the original BMB report. In summary: "Hairy Cell Leukemia, extensive involvement (approx. 70%)." This means that 70 percent of my bone marrow is hairy cells. Although extensive, this isn't necessarily very high as far a treated cases of HCL go. It's not uncommon for patient's to have 90% involvement. My marrow still had plenty of "areas of preserved hematopoietic (stem cell) marrow present, including megakaryocytes (platelet precursors), erythroid, and myeloid cells. "Diffuse mild to moderate reticulin fibrosis [was] noted." These are strands sent out by the hairy cells that bind and pith the infiltrated marrow. This characteristic becomes more prevelant as the disease progresses. It will all resolve with the chemotherapy.

By the time I found the LabCorp pathologist contact information on the report, the other bone marrow core slides had finally arrived at NIH. My quest to find the original H&E stained core slide was no longer required, so Christi and I headed up to NIH. It took the better part of the afternoon before I was finally approved to enter the trial. I made one final trip to phlebotomy. Pete Townsend's "Give Blood" was playing in the background. Okay not really, but it was playing in my head. Once back in the clinic, I read and signed the protocol consent form and then waited to be randomized.

Randomized for Cladribine-only for the initial treatment with Rituximab to follow 6 months later at the onset of minimum residual disease (MRD), I was treated on an outpatient basis in the "day hospital". The IV insertion was easy. I had to wait with a saline drip while the initial prescription was filled. I verified the dosage rate, my mass and total dose in the IV solution at .15 mg/kg/day, 92 kg and 13.9 mg. The nurse set up the drip console settings, and I was off and running.

Treatment started at 5:25 pm. It took about 2 hours 10 minutes for all the Cladribine to drip into my veins, but I didn't feel any side effects or sensations. I ate while being treated, but the food was really awful, so when the treatment was over, Christi and I headed over to Jaleo to get tapas. (tapas always has a really good variety of gluten free low sugar menu items).

It's been 5 1/2 hours since Chemo started and, if anything, I feel as good or better than I did then. I'm sure the relief of not experiencing side effects has helped. I'm sure I'll feel worse in a few days.

Overall, it was a long but boring day...
and boring is good.

I'm hungry again...
and hungry is good too.

Big Day Tomorrow

2009-04-21T18:51:00.000-07:00

All the major testing is done. I go up to NIH tomorrow at 1:30 with luggage in tow. They ordered some last minute blood tests for tomorrow before my clinic appointment with Dr. K at 2:30. That appointment is the last gating factor before I can be admitted and treated in the trial. If accepted, I'll then be told whether I randomized to Cladribine and Rituximab or Cladribine only, then the PICC will get installed. Fortunately, I was just told that I don't have to fast for the blood test and only have to fast 6 hours before the PICC is installed, so I can finally eat breakfast again.

If all goes well, I may only have to stay in the hospital for 2 days, then return home and do the remainder of the drug treatments on an outpatient basis.

Today's tests included an abdominal ultrasound. The lab technician was superb -- very fun to talk to and she liked explaining the physics of the device as she made the measurements. She told me how they can peform vascular exams with ultrasound now -- avoiding the IV contrast and radiation that were previously required with the CT scan. She examined the liver, spleen, kidneys, and gallbadder. My spleen measured over 1 cm smaller on the ultrasound than it did on the CT scan nearly 3 weeks ago. This was probably just due to the way I was positioned, but wouldn't it be great if it were due to a reduction in sequestered hairy cells?! I may never know for sure, but I'll ask Dr. K if that is a normal variance.

The coolest test had to be the echocardiogram -- it's basically an ultrasound of the heart. I got to see my valves moving and heart muscles pumping. It was fascinating technically, but didn't compare to the emotional rush the first time I saw Claire's heartbeat.

I want to thank everyone for all the well wishes, prayers and loving gestures you have made. They've truly humbled me, and I'm forever grateful. I can feel the energy of your prayers and thoughts and I know they are working. Regardless of our personal religious beliefs, we all share a common devine energy through our prayers and love for each other, which unites us as one family. I am blessed to have all of you as part of mine.

Love to all
Sola Virtus Invicta!

Buckets 'O Fun

2009-04-20T17:52:00.000-07:00

You knew I was going to make that the title for this post, didn't you? Among other things, I got my urine buckets today. In the immortal words of Forrest Gump, "That's all I've got to say about that."

Over the past month, my blood counts' declines are much less compared to the large decrease I experienced in February (relatively speaking), so I think my nutrition changes have helped slow things down. Platelets are at 83, and I haven't felt lightheaded in days, so I'm happy about that. My absolute neutrophil count is still above 1.25 but continuing to decline, so I'm anxious to get started with chemo before the chance of infection gets any worse. Urinalysis and blood chemistry were nearly perfect.

I didn't have to do a CT scan today because the prior one ordered by my hemonc was good enough for study purposes. The less radiation the better. My chest X-ray was typical for someone my age, and I haven't seen my EKG results yet. Total elapsed time for the EKG was about 3 minutes. It took longer to hook up all the probes than to make the measurement.

Total cholesterol is at 120, with HDL (good chol.) at 28 mg/dL and LDL (bad chol.) at 55 mg/dL. Compared to 30 and 85 on February 5th, it looks like my hairy buggers are having a roto-rooter feast, but of course my diet is very different now from what it was then. On the bright side, I suppose my pipes will be clean once I recover. It'll be interesting to see where these numbers go 6 months after chemotherapy.

I'm keeping this one quick. I go back tomorrow to turn in the bucket, get my abdominal ultrasound and an echocardiogram.

T-1 day and counting...

The Workup

2009-04-17T18:45:00.000-07:00

Next week's schedule arrived yesterday and it's quite a workup.

Starting midnight on Sunday, there's to be no eating and only moderate drinking of water. I've an appointment at the Phlebotomy lab at 9 am Monday morning for some more blood letting followed by a visit to ... The 13th Floor (pretend that text is undulating like the credits for a scary movie) where they'll sample my blood for hairy buggers. I've got a surprise waiting for them, though. You see I replaced my regular blood with Folger's instant crystals. They won't believe it's an instant!

After the blood letting, nurse R will bring me my "urine bucket". Oh joy! I get to collect pee for 24 hours to make sure my kidneys are functioning properly. Even if I could head back to work for a half day, I don't think the logistics of the "urine bucket" would work out too well. Right now, disturbing images of the homeless guy from "In Living Color" and his "pickle jar" are racing through my brain. Those of you who know what I'm talking about just had a disturbing laugh. Those of you who don't should be thankful. I just hope the bucket has a lid.

At 9:40, I head down to Radiology, chug a quick mix of strawberry flavored Barium (note: based on prior experience, it tastes more like @*!) and then get my CT scan. They'll inject contrast agent into my vein right before I go into the imager -- makes you feel all warm and cozy inside. I'm not a stranger to CT scans. I had my first one back in 1991 shortly after suffering debilitating migraines right after my first wedding. Funny how they started upon getting married and stopped after getting separated. Seriously though, I think it was the damn Liz Claiborne perfume she wore.

Next, I get an EKG. I've always wanted one ever since seeing episodes of Emergency! as a kid. I just thought the circumstances would be a bit more heroic, you know -- like collapsing after saving a bus full of orphans from falling off a cliff while Johnny Gage and Roy DeSoto show up just in the nick of time.

Monday wraps up with a chest X-ray. I expect my skin will soon glow in the dark with all the radiation I've gotten over the past two months. On the bright side, I won't have to turn on the light to fill my urine bucket in the middle of the night...

Tuesday isn't quite as busy. I start off with a ultrasound of my abdomen at 9:00 to check out the old spleen, followed by one last pee in "Ye Olde Urine Bucket" before handing it back to nurse R. I head over to Building 5 at 11 for an echocardiogram, then I'm done for the day.

On Wednesday, I suffer without food until I meet with Dr. K at 2:30 for my physical. If all goes well, I'll get admitted and the PICC line will get installed at 3:30. The meds will be administered shortly thereafter. If I'm selected for Rituximab, it will be injected first over about 4 to 5 hours, followed by the Cladribine. So far the other patients have had slight fevers and shortness of breath, but nothing too serious. After that, I hang out and get daily injections of Cladribine for 4 more days. If there are no serious effects after day 3, I may switch to outpatient for the last 2 days.

If selected for Rituximab, I'll head back to NIH once a week for 2 months to get those injections. CBC's will be measured weekly until July. Bone marrow biopsies, and standard image sets will be run once every 6 months for some time thereafter.

GSE, JNK activation and apoptosis

2009-04-13T19:40:00.000-07:00

I saw some articles on the cell death effects of Grape Seed Extract (GSE) on Jurkat cells through increased activation of JNK enzymes in these leukemic T-cells. This peaked my interest, so I did a little more research on JNK activation in HCL and GSE.

Based on research by Kamiguti, Harris, Cawley, et al, (University of Liverpool School of Cancer Studies) it appears that HCL cell survival is in large part "determined by the balance between the potential proapoptotic effects of p38/JNK and the antiapoptotic ones of ERK." In layman's terms, ERK is an enzyme in HCL that tries to keep it alive, and JNK is an enzyme that tries to help it die; the balance between the two enzymes plays a large role in whether the cells live (antiapoptotic) or die (proapoptotic). (Apoptosis = cell death by suicide -- typically through the TP53 tumor suppressor gene, but other genes and proteins can also induce it).

Their research showed that another family of enzymes known as PKC was present in HCL and helped increase ERK and decrease p38/JNK. By using PKC inhibitors in conjunction with 2-CdA chemotherapy, they improved the chemo's effectiveness.

Getting to the point: By activating JNK enzymes in HCL, the ERK to JNK ratio will favor HCL cell death. Prior studies of GSE in Jurkat cells as well as prostate cancer show that GSE is highly effective in activating JNK enzymes and inducing apoptosis in those cell lines. This suggests that a natural remedy like GSE may hold promise for being an effective proapoptotic agent in HCL. I hope some universities will realize the potential of GSE for JNK activation in HCL and investigate it further.

Drawback: GSE is a potent blood thinner; thus, regular use of GSE could cause excessive bleeding in individuals with Thrombocytopenia or anyone taking blood thinners; hence, taking GSE directly without medical supervision could be extremely dangerous and possibly lethal for anyone with clinical HCL.

Additional Note: Aloe-Emodin, found in Rhubarb and Aloe, is also a pronounced JNK activator and apoptosis agent. Rhubarb is also a known blood thinner which could cause spontaneous bleeding in individuals with Thrombocytopenia or clinical HCL.

PET Scans, Sugar and Leukemia

2009-04-13T17:51:00.000-07:00

After noting some of the differences between the biochemistry of leukemia versus solid tumors, I had questions regarding whether leukemia is really a sugar feeder like solid tumors are. This article on PET scans confirms that it is. Check out the image on the left of the article. It's a PET scan of a leukemic patient.

PET scans operate by adding a radionuclide to a glucose analogue sugar and then imaging the areas where consumption/decomposition occurs, causing photon emission -- the anaerobic cancers. Since this approach can image leukemic infiltration of bone marrow, it demonstrates that leukemia is also a sugar feeder.

http://www.durangoherald.com/sections/Features/Health/2009/03/09/Does_chemotherapy_work/

Note: studies of HCL indicate that it does not appear prominently in PET scans; hence, less dependent on sugar as its fuel.

'Shrooms and Stuff

2009-04-12T06:00:00.000-07:00

Bummer. I started taking medicinal mushrooms in the hope that it would stimulate certain anti-cancer cytokine production including tumor necrosis factor (TNF) and various interleukins by my immune system to see if that would reduce the HCL tumor burden; however, it looks like HCL may actually proliferate in the presence of TNF based on research by Barak, Nisman, et al (see Tallman and Polliack, 'Hairy Cell Leukemia', pp. 107 - 123). Using mushrooms (or any other method) to secrete more of these cytokines may be a bad thing.

This same research indicates that hairy cells may have a decoy IL-1 (interleukin) receptor which binds IL-1 without inducing any effect, and "soluble IL-2 receptor levels were shown to correlate well with HCL tumor burden and disease activity...while levels clearly decreased during therapy [with Cladribine] and after clinical response."

There are many other interesting facts in this research article. In fact, hairy cells appear to secrete TNF and shed TNF receptors into the bloodstream. TNF has been measured in large quanities in HCL patients.

Conclusion: Unlike other cancers, it may be a bad idea to try to increase your body's TNF and interleukin production if you have HCL. HCL is very unlike other cancers and expresses a biochemistry which is uncommon and may proliferate in the presence of certain cytokines.

Per the April 9 test at my hematologist, my blood counts have not changed significantly, but that report did not include the level of differential detail needed to compare it to the tests run by NIH.

New results from the March 31 test: Dr. K evaluated the binding capacity of certain proteins expressed on the surface of the hairy cells (CD20, CD22 and CD25) to monoclonal antibodies being researched. The mean number of molecules of anti-CD20 bound per hairy cell was greater than 100,000. The mean number of molecules of anti-CD22 and anti-CD25 bound per hairy cell was 58,656 and 14,103 respectively. This bodes well for treatment with Rituximab (the anti-CD20 drug being used in my trial) as well as RL22 and HA22 (other drugs being researched by Scripps and NIH).

My neck and thoracic MRI from April 2nd showed some slight degeneration of the disc between my C5 and C6 vertebrae. This is the most common degeneration for any adult. The bone marrow signal is heterogenous (abnormal intensity) because I have HCL, but the spinal cord signal "shows normal intensity with no evidence of abnormal enhancement." No well defined lesions were identified. Nothing too unusual for someone with HCL.

One more week before the final round of testing and chemo begin.

Nutrition

2009-04-05T15:43:00.000-07:00

At any given time, everyone has hundreds if not thousands of cancer cells in their body -- sun damaged skin cells, a kidney cell mutated by aspartame as it decomposes into methanol and formaldehyde in your digestive system. The list is endless. Normally, the body's immune system recognizes and kills the mutant cells before they can establish themselves. But cancer thrives on sugar, and a diet low in essential nutrients and high in glucose and added sugar gives the normally hapless enemy every advantage to grow its army and attack the body while leaving your immune system too weak to properly defend itself. That's basically what happened to me as I worked late hours at the office subsisting on M&M's and Mountain Dew. Coming home too tired to make a real meal, I'd turn to a frozen pizza loaded with nitrates, followed by scoops of sugar and fat-laden vanilla ice cream. This high-glucose fuel allowed the cancer to move from its impersceptible chronic phase to the more symptomatic phase.

I'm not saying don't enjoy the good things in life, but I am saying don't abuse them or your body for the sake of convenience. My perception of what the good things really are certainly has evolved in a short time. We all know that good nutrition is fundamental to preventing cancer, but often assume that as long as the ingredients have some form of natural origin we'll be okay. Unfortunately, avoiding Twinkies, soda pop and food that doesn't decompose or grow mold is not good enough. Even when relying on all-natural ingredients, the nutrient/sugar ratio of our diets plays a fundamental role in determining whether we'll get cancer and whether we'll beat it if we get it. These concepts are best described in Patrick Quillin's "Beating Cancer with Nutrition".

Regarding sugar: I'm trying to minimize it, not replace it. I was surprised to see that since Aspartame's (aka Equal/Nutrasweet) introduction in 1980, there has been a 280% increase in the rate of occurence of brain tumors. Given the plethora of cultural changes that have impacted our lifestyles and environment over the past 3 decades, Aspartame can't be given the full blame for the increase, but it is interesting to note that during the FDA approval process, several scientists protested approval because of the high rate of occurence of brain tumors in lab rats consuming Aspartame (wiki Aspartame). Based on current research, Splenda appears to be the safest alternative artificial sweetener and Stevia appears to be a safe natural alternative. Still, I prefer to just reduce sugar and avoid alternatives altogether.

Now that I have cancer, a fundamental nutrional lifestyle change has occurred. No more ice cream (at least until I go into remission -- and then it will be a rare occasion), no more soda, no more candy, and I minimize processed foods and foods with a high glycemic index (like white potatoes and processed rice and potato flour). Sometimes I eat salad for breakfast, but usually it's yogurt with a side medley of peppers, onions, garlic and oriental mushrooms sauteed in olive oil. Top it off with a fried eggwhite, vitamin and herbal supplements (A, C, D, kelp, magnesium, chromium, cinnamon, ginger) and a cup of tea. I drink Rooibos tea two to three times daily, keep a supply of fresh vegetables ready for snacking in the refrigerator, and have a bowl of sunflower seeds sitting on the counter at all times. Vitamin C is similar to sugar in its molecular structure and in high quantities is able to fool cancer cells into trying to consume it as fuel -- resulting in apoptosis of the tumor cells.

Among the foods I've added to my arsenal are quinoa, the most nutritious of the whole grains, and cancer fighting oriental mushrooms like agaricus blazei, reishi, shiitake, and maitake. Update (4/12/09 -- *** WARNING *** using mushrooms to increase cytokine production such as TNF may enhance the proliferation of HCL. See post from 4/12/09 and Tallman, pp. 107-126). All of these have undergone testing that shows they inhibit tumor metastasis and the progression of various leukemias. If they're good enough for the Memorial Sloan-Kettering Cancer Center, they're good enough for me.

At this point, 25% of you think I'm nuts, 50% of you confirmed your prior suspicions, and 20% are thinking even if you wanted to do that, there's no way you could. The other 5% had already confirmed I was nuts long ago. When you have cancer, there's not much you can control, and many of my fellow HCL'ers choose not to control anything -- just take the chemo, go into remission and wait. I choose to control my diet and treatment, and so far it's proved beneficial. My counts have stabilized and in many cases improved. My dizzy spells are less frequent and my endurance has improved. I see my hematologist this Thursday for another CBC. Let's hope the results show continued improvement so that when I go in for chemo, my immune system's arsenal will be fully prepared to defend the good cells while letting the chemo do its job against the bad ones. I believe that these dietary changes are a lifetime commitment -- required to minimize the proliferation of the disease after chemo, maximize the period between recurrance and increase the possibility of organic eradication.

One last note: hairy cell leukemia also consumes cholesterol. Several studies have shown that hairy cells contain more cholesterol than their normal B-cell counterparts. Likewise, patients with hairy cell leukemia typically have low levels of both LDL (bad) and HDL (good) cholesterol. My HDL had been lower than normal for several years prior to my diagnosis. Even with lack of exercise, it was considered low. I took fish oil pills for two years with little improvement. My LDL level dropped suddenly as the disease progressed and symptoms increased. I'm going to ask my hematologist to run a cholesterol test this Thursday to see if the level has continued to drop. Typically, an abnormally low level of bad cholesterol is not dangerous although it is a marker that a causitive disease, such as HCL, is present. It's also associated with a higher than normal incidence of stomach cancer.

Note: Going on a low cholesterol diet during treatment to try to starve HCL is probably a bad idea since many studies indicate that cholesterol is a necessary agent in B-cells to induce apoptosis (cell death via suicide).

NIH and Chemotherapy

2009-04-01T16:48:00.000-07:00

Yesterday, March 31st, Christi and I headed up to NIH to do my initial blood screening and talk to one of the study nurses about study details and logistics.

During the trip in the car, Christi read through the trial description and all the drug warning information on Rituximab. Looks like we'll have to put off trying to have another kid for a year, but that's okay, I think we'll want things to settle down before we try again anyway. Risk of sterility is a possibility with the chemo, but I've already mitigated that issue.

NIH is a huge facility. There are probably 90 buildings overall. We headed to Bldg. 10, the Clinical Center, which is probably the biggest building on the campus. I was overwhelmed initially. NIH is a secure facility. When you arrive, you have to enter at the visitor gate, exit your vehicle, which is searched for contraband while you go through a security line like you're at an airport. Anyway, once I got to the Clinical Center, I headed to the Phlebotomy Lab where they drew my blood. It's a busy place. First you get in line and get a number, like at the DMV, then you sit and wait for your number to be called.

Once they call you, you're directed to one of 10 lab stations. Once seated, you feel surrounded -- every sense amplified. My orders hadn't been received yet, so the technician left me in the booth and left to track them down while I listened to the little guy 3 booths down scream in terror as his blood was drawn. Nothing you hadn't heard before at the physician's office, but somehow being there just increased your level of sympathy. He passed my booth as he was leaving, tears running down his face, and I could see how all the blood vessels in the skin of his checks were visible to the naked eye -- his skin thinned and reddened, not from his screaming but from his underlying condition.

After 10 minutes, the technician returned with my orders, pulled 7 green tubes and 1 purple one. Once all the tubes were filled, she handed me a bag with the 7 green tubes and said "You need to take these to the clinic on the 13th floor." What kind of hospital has a 13th floor? Don't they know that's bad luck? That's why all the hotels go from 12 to 14, skipping 13!

Once we got to the 13th floor, I entered the clinic, went up to the desk and said "The lady downstairs said you'd give me $20 for this bag of blood" to the man and woman seated there. He smiled and said, "$20, is that all? You should hold out for $100", then the lady next to him told me to take it down the hallway and put it on the counter next to the sink in the room on the right.

I dropped off my blood, then called one of the study nurses to let her know I was there. Two of them showed up -- nurse R and nurse B. After introducing ourselves, nurse B headed off and nurse R stayed to discuss the trial and answer our questions. After talking for awhile, nurse R retrieved the CBC results. My platelets had improved over the past week, climbing from 85 to 99. That was very exciting to me. Maybe my low sugar diet and supplements are working. The white blood count (WBC) had dropped, which startled me at first, but then I thought "The WBC includes the hairy cells, so maybe the drop is because there isn't enough sugar to feed them all" (cancer is a sugar feeder). Wishful thinking, I know, but anything is possible.

We discussed the study protocol. Since my platelets are below 100, I qualify for further evaluation and testing. These include MRI, CT scan, echocardiogram, etc. I go in for the MRI tomorrow night at 8:30. The others will be run from 4/20 to 4/22. If I pass those tests, then I'll be admitted on the 22nd and go through 5 days of chemo. The study is randomized, so I may or may not receive the Rituximab. I'm opting to go in-patient because it's their standard practice and I fear that rocking the boat may cause chaos. Likewise, once I'm an in-patient, short-term disability will kick in right away, and the logistical issues surrounding my low WBC from chemo and Claire's daily germ party at day care will be eliminated.

The chemotherapy, a drug called Cladribine (aka 2-cda), is going to knock down all my blood counts and make me prone to infections for a few days, but if I don't get treatment, I'll either hemorage to death or get a fatal infection anyway. Unlike the 24/7 slow drip approach that my hematologist uses, the NIH study is going to use an IV infusion. They'll still install a peripherally inserted central cather (PICC) from a vein in my bicep up to my heart so that my vein won't be damaged by the drug's toxicity. The volume of blood in the heart will act to immediately dilute the drug as it enters. The drug will be administered over 5 days, 4 hours per day. Based on posts from patients who've gone this route, I'll feel very lethargic by the 3rd day as my RBC goes down. Most patients experience a high fever (~100) as their white blood cells are destroyed. This lasts about 48 hours. Very few infections have been documented, but they do happen, and are largely responsible for the 3% fatality rate associated with Cladribine. Yet another reason why I'd rather be an in-patient.

Once the chemo is done, I'll head home and rest for another week. nurse R wasn't sure how long it would take before I could return to work. It's largely based on how long it takes for your WBC to get above 2.0. I'll ask some fellow HCL'ers what their experience has been and let you know.

Anyway, the good news is that for the most part, my blood counts appear to have stabilized or improved with the change in diet and supplements, and it looks like I'll be entering the trial on the 22nd if all goes well. If my blood counts were to show more visible improvement, I'd have to think twice about going through chemo. Let's hope this is the case. Once I finish compiling my recent data, I'll discuss it in detail in the next blog.

Cheers

Diagnosis and Prognosis

2009-03-29T05:24:00.000-07:00

After several months of symptoms and numerous doctors visits, I was diagnosed with Hairy Cell Leukemia (HCL) this past Friday (3/27/2009).

As far as leukemia goes, HCL has a good prognosis. 80% of patients go into complete remission after standard chemotherapy (Cladribine), and relapse usually doesn't occur for anywhere from 3 to 12 years. 10% go into partial remission and 5% don't respond. Two other standard therapies include Pentostatin (another chemo) and interferon. Rituximab and BL22 are also being used, so there are lots of approaches available should one not do the job.

HCL is an uncommon neoplastic (malignant) disorder of B lymphocytes (a type of white blood cell) that afflicts middle-aged men. The patient usually presents with pancytopenia (broad spectrum reduction in blood counts -- low platelets, low white blood cells, low red blood cells). There are 500 to 800 cases of HCL annually, representing just 2% of all leukemias. Nevertheless, HCL has been highly researched because it is very treatable and acts as a research catalyst for finding drugs to treat more difficult diseases.

When I went in for my physical in October, 2007, my doctor noted that my platelets were low and that I should check back in 6 months. Work got really busy and even though I was feeling lousy and irritable (dizziness, nose bleeds, insomnia), I attributed it to overwork and poor diet and put off going back to the doctor until this February. Often, I would discuss how lousy I felt with Christi and how I should go to the David Drew Clinic and get checked out head to toe. We had family photos taken in November, and when I saw how gaunt I looked, I knew there was a something wrong. She hung one of the pictures in the hallway and I commented "I hate that picture, it makes me look like I have cancer," but I kept putting off going to the doctor because I didn't think I had the time. Stupid.

I tried to schedule a Dr.'s appointment in December using their on-line appointment service, but they kept calling my home phone instead of my cell to schedule it even though I told them to call my cell phone. After I started feeling dizzy more and more often while sitting down, I finally took the half-hour to wait on the phone, speak to a human being and schedule the appoinment. My regular doctor wasn't available for another 6 weeks, so I scheduled to see a new doctor who was available in 10 days (early February).

At the February physical, CBC results were not good. My platelets were below normal (118) and my WBC was at the low end of normal. My doctor told me to come back in 3 weeks and test again. Needless to say, I stopped working so hard and put my health and family back into perspective.

After 3 weeks, my Dr. ran a differential blood test which confirmed I had thrombocytopenia and absolute neutropenia (low neutrophils -- the white cells that are the first line against infection). Needless to say I was freaking out doing my own differential diagnosis. The hematologist my doctor recommended wasn't available to see me for 5 weeks, so I found another and I'm glad I did. He saw me in 10 days, drew lots of blood and scheduled a follow up appointment for 3 weeks. During that time, he examined my blood and found some characteristics which led him to run a panel for leukemia.

Within a week, his office called to move up my follow-up appointment to discuss what they found. The day after my birthday, I met with him and he presented the results. The phenotype indicated HCL. He did a great job in delivering the news and letting me understand that a BM biopsy was needed to confirm the Dx and that if it was HCL, the prognosis is good and what the treatment would be.

While I ran over to my endodontist to fix a root canal that my dentist completely botched (actually he never found that I had a second dead tooth behind the one he treated) and had remain infected for two months while he just gave me antibiotics, my HemOnc went out of his way to schedule me for a bone marrow biopsy later that morning. I returned to his office and got it done. It wasn't bad. The most painful part was when the needle was removed. The initial tap was dry (typical for HCL) so he went back in with a needle to extract the marrow. I rested, watched the tech prep the slides (marrow is like jelly), then went home for the rest of the day. My doctor also ordered a CT scan with contrast to check for splenomagoly (enlarged spleen), which is a typical symptom of HCL, and any signs of lymph node enlargement (which might indicate lymphoma or other cause). I had the CT scan done the following Wednesday.

Concurrent to these events, I found that I had developed gluten intolerance. For many years, I noticed that typically after eating, I experienced dizziness and itchiness. Likewise, my state of mind was like an emotional roller coaster -- lots of anxiety, paranoia and irritability. My digestion habits were a complete mess and had been for several years. Upon switching to a wheat-free diet, most of my gastro-intestinal problems went away (volume and frequency decreased, no more itchy skin, diarrhea, etc), and my anxiety has ceased to exist. It's made dealing with the HCL much easier.

After the bone marrow biopsy, I started researching HCL in detail, and sent an email to NIH study nurses regarding trials for HCL. I received a prompt reply from Dr. Robert Kreitman, Chief of the Clinical Immunotherapy Section at NIH, regarding a new trial which combines the standard chemotherapy with a biological therapy using the monoclonal antibody Rituximab. I believe the ultimate goal of this treatment is to eradicate/cure the disease -- wiping out every instance of the hairy cells so they can no longer reproduce. The objective stated in the trial summary is "To determine if cladribine and rituximab, whether given together or with rituximab given 6 months after cladribine, is effective in treating residual hairy cell leukemia (disease that remains after the original treatment)."

(My rambling thoughts and overanalysis:) I think this trial is based on the theory that hairy cell starts as a single mutation to one cell which then proliferates exponentially over time. Regardless, if all hairy cells are killed, the body won't produce more unless it is again exposed to mutanagenic toxins (organic solvents like Xylene) and another cellular mutation occurs. Thus, if your hairy cells grow at a known rate before the trial, then one can expect a certain population density to exist in the marrow after several months if residual disease still exists after therapy. If no cells are found after several months, then the disease may in fact be eradicated/cured. I'll ask Dr. K if any of this is correct if he's willing to entertain me on the subject and update or delete it accordingly. Needless to say, I won't be photo-etching my own home-brew circuit boards ever again, and I'm glad I moved from my old house where perchlorethylene (PCE) had leached into the well water (probably from the Texaco up the street dumping degreasing agent into the ground). The county found this after I moved and never bothered to tell me. Nice, eh? At this point, it doesn't really matter how I got it. What's important is that I mitigate or eliminate it.

As you now know, the bone marrow biopsy confirmed the HCL Dx. I'm going to NIH on Tuesday to draw blood that will verify whether I qualify for the trial, discuss concerns and the overall schedule. The most important test will be to see if and how quickly my hairy buggers clone themselves. This is necessary to confirm eradication as the study progresses. If they can't fit me in within 3 weeks, I'll procede with standard Cladribine therapy with my HemOnc.

I'll keep you updated as things move along. My next post will likely discuss the details of chemotherapy and nutrition to slow the cancer and keep it at bay. If nothing else, this has been a wakeup call to eat right, prioritize my life and take better care of myself.

By the way, most of the early research on HCL was done at Ohio State University, starting with its breakthrough discovery in 1958 by Dr. Bertha Bouroncle. My dad would be very proud. Go Buckeyes!